Methods, systems and devices for reducing the luminal surface area of the gastrointestinal tract

ABSTRACT

Methods, systems and devices for treating a patient include providing a tissue treatment element constructed and arranged to deliver energy to tissue and treating tissue of the gastrointestinal tract by causing the tissue treatment element to deliver energy to an energy delivery zone. Treatment results in a reduction in the luminal surface area of at least a portion of the gastrointestinal tract. In particular embodiments, the methods, systems and devices are used to treat diabetes.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of International PatentApplication No. PCT/US2014/040957, filed Jun. 4, 2014, which claimspriority under 35 USC 119(3) to U.S. Provisional Patent Application Ser.No. 61/831,025, entitled “Methods, Systems and Devices for Reducing theLuminal Surface Area of the Gastrointestinal Tract”, filed Jun. 4, 2013,which is incorporated herein by reference by its entirety. Thisapplication is related to: U.S. patent application Ser. No. 13/945,138,entitled “Devices and Methods for the Treatment of Tissue”, filed Jan.18, 2013; International PCT Application Serial Number PCT/US2013/28082,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Feb. 27, 2013; International PCT Application SerialNumber PCT/US2013/37485, entitled “Tissue Expansion Devices, Systems andMethods”, filed Apr. 19, 2013; International PCT Application SerialNumber PCT/US2013/052786, entitled “Electrical Energy Ablation Systems,Devices and Methods for the Treatment of Tissue”, filed Jul. 30, 2013;International PCT Application Serial Number PCT/US2013/054219, entitled“Ablation Systems, Devices and Methods for the Treatment of Tissue”,filed Aug. 8, 2013; and International PCT Application Serial NumberPCT/US2013/063573, entitled “Methods, Systems and Devices for PerformingMultiple Treatments on a Patient”, filed Oct. 7, 2013; the contents ofwhich are each incorporated herein by reference in their entirety.

TECHNICAL FIELD

The embodiments disclosed herein relate generally to systems, devicesand methods for treating tissue, particularly gastrointestinal tissue.

BACKGROUND

A number of systemic diseases are currently treated with medicines thatprovide amelioration of symptoms or complications of the illnesses butwhich do not specifically target the pathologic basis of disease. Theseillnesses are characterized as “chronic diseases” for no reason otherthan the fact that, for the majority of patients, the diseases arechronically managed rather than acutely treated.

The reasons that chronic diseases are not treated definitively differbased on the specific diseases in question. In some cases, the diseasesare not understood well enough as of yet for definitive therapies tohave been developed to solve them. In other cases, the definitivetherapy, if it does exist, is too unattractive (e.g. high morbidity ormortality, high risk of complications, inaccessible) for the majority ofpatients to achieve therapeutic relief. In either case, chronicmanagement of the illness burdens the patient with the need for ongoingmedical attention and burdens the healthcare provider and system tocontinue to deliver episodic (and expensive) care of chronic diseasesand their complications.

Diabetes is a metabolic disease in which a person develops high bloodsugar because the person's body does not produce enough insulin or thecells of the body are incapable of effectively responding to theproduced insulin. Primarily, diabetes is of two types: Type 1 and Type2. Type 1 diabetes results from the body's autoimmune destruction ofpancreatic beta cells and, consequently, the body's failure to produceenough insulin. Type 2 diabetes is a complex metabolic derangementrelated to obesity that causes hyperglycemia through insulin resistance(in which the body's cells fail to properly utilize the producedinsulin) and eventually inadequate insulin production to meet the body'sneeds.

Currently, there are several procedures aimed at treating diabetes basedon the above concept. The procedures require major surgery, removal ofportions of the gastrointestinal (GI) tract, and/or long-term implants.As with any major surgery, gastric bypass surgery carries a risk ofcomplications.

Devices have been developed to delivery energy to the body. For example,cardiac ablation devices have been designed to delivery ablative energyto coronary tissue. Additionally, urethral resection devices have beendesigned to burn or cut away portions of a prostate. Each of thesetechnologies has been modified and adapted toward effective usage in theparticular portion of the body to be treated as well as the particulardisease to be treated.

New inventions that can harness novel physiologic understanding ofdiseases and deliver therapies that are therapeutically beneficial,accessible to patients, and reduce healthcare costs are needed.Specifically, there is a need to provide a therapeutic treatment ofpatient diseases and disorders such as diabetes, with a procedure in theGI tract that is simple, and minimally invasive, and has otheradvantages for patients.

SUMMARY OF THE INVENTION

According to one aspect of the present inventive concepts, a method fortreating a patient comprises providing a tissue treatment elementconstructed and arranged to deliver energy to tissue, and treatingtarget tissue of the patient's gastrointestinal tract by causing thetissue treatment element to deliver energy to an energy delivery zone.The method causes a reduction in the luminal surface area of at least aportion of the gastrointestinal tract.

In some embodiments, the patient is a human being.

In some embodiments, the surface area reduction comprises a reduction inmucosal surface area.

In some embodiments, the surface area reduction is constructed andarranged to reduce absorption and/or secretion of the at least a portionof the gastrointestinal tract.

In some embodiments, the method treats diabetes such as type 2 diabetes.The method can treat one or more of: a patient that has exhibiteddiabetic physiology for less than 1 year; a patient that has exhibiteddiabetic physiology for less than 2 years; a patient that has exhibiteddiabetic physiology for less than 5 years; or a patient that hasexhibited diabetic physiology for less than 10 years.

In some embodiments, the patient has exhibited a disease state to betreated for at least 1 year, at least 2 years or at least 5 years.

In some embodiments, the method treats impaired glucose tolerance.

In some embodiments, the patient comprises a patient with an HbA1c levelof at least 7.5 or at least 8.

In some embodiments, the method treats a disease or disorder selectedfrom the group consisting of: diabetes; pre-diabetes; impaired glucosetolerance; insulin resistance; and combinations thereof.

In some embodiments, the method treats a disease or disorder selectedfrom the group consisting of: diabetes; pre-diabetes; impaired glucosetolerance; insulin resistance; obesity or otherwise being overweight;hypercholesterolemia; exercise intolerance; psoriasis; hypertension;hypertriglyceridemia; metabolic syndrome; and combinations thereof.

In some embodiments, the method is constructed and arranged to cause areduced absorptive and/or secretory capacity in a surface area reducedportion of the gastrointestinal tract, such as when the reducedabsorption is a reduced absorption of glucose, cholesterol, amonoglyceride and/or a fatty free acid.

In some embodiments, the method is constructed and arranged to reduceglucose absorption in a surface area reduced portion of thegastrointestinal tract after food intake.

In some embodiments, the method is constructed and arranged to reducerelease of gut hormones from a surface area reduced portion of thegastrointestinal tract after food intake, such as to cause reducedrelease of GIP and/or other proximal gut hormone.

In some embodiments, the surface area reduction results in a physiologicchange in a surface area reduced portion of the gastrointestinal tractselected from the group consisting of: reduced absorption of nutrients;reduced secretion of gut hormones; and combinations thereof.

In some embodiments, the method comprises a second patient treatment.The second patient treatment can be performed after treating the targettissue in the first treatment. The second treatment can comprise acontrolled diet, such as a low calorie diet. The low calorie diet cancomprise one or more of: a diet of less than 1500 calories per day; adiet of less than 1000 calories per day; a minimal fructose contentdiet; a minimal simple sugar content diet; a minimal fat content diet;and a diet performed during a period a mucosal regrowth. The secondtreatment can comprise a pharmaceutical treatment comprising apharmaceutical selected from the group consisting of: ananti-inflammatory agent such as a steroid; an immunomodulator such asSirolumus or Tacrolimus; Sucralfate; a bismuth compound; an acidinhibitor; a proton-pump inhibitor; a H2-receptor blocker; anantibiotic; an anti-fungal; an appetite suppressant agent; ananti-obesity agent; an anti-cholesterol agent; a diabetes drug;metformin; a GLP-1 analogue; a DPP-IV inhibitor; sulfonulereas; insulin;an insulin analog; and combinations thereof.

In some embodiments, the energy delivery zone and/or the target tissuetreated is proportionally related to the longevity of the disease state.In these embodiments, the disease state can be diabetes. The energydelivery zone can comprise less than 50% of the duodenal inner surfacearea if the patient has exhibited diabetic physiology less than 3 years,such as when a portion of the energy delivery zone receives energy fromthe tissue treatment element, and the portion receiving energy comprisesa percentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.The energy delivery zone can comprise less than 50% of the duodenalinner surface area if the patient has exhibited diabetic physiology lessthan 5 years, such as when a portion of the energy delivery zonereceives energy from the tissue treatment element, and the portionreceiving energy comprises a percentage of the energy delivery zoneselected from the group consisting of: at least 2%; at least 5%; atleast 10%; or at least 20%. The energy delivery zone can comprise lessthan 75% of the duodenal inner surface area if the patient has exhibiteddiabetic physiology less than 7 years, such as when a portion of theenergy delivery zone receives energy from the tissue treatment element,and the portion receiving energy comprises a percentage of the energydelivery zone selected from the group consisting of: at least 2%; atleast 5%; at least 10%; or at least 20%. The energy delivery zone cancomprise less than 75% of the duodenal inner surface area if the patienthas exhibited diabetic physiology less than 10 years, such as when aportion of the energy delivery zone receives energy from the tissuetreatment element, and the portion receiving energy comprises apercentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.

In some embodiments, the energy delivery zone and/or the target tissuetreated is proportionally related to the severity of the disease state.In these embodiments, the disease state can be diabetes. The energydelivery zone can comprise less than 50% of the duodenal inner surfacearea if the patient has an HgBA1c level less than 8, such as when aportion of the energy delivery zone receives energy from the tissuetreatment element, and the portion receiving energy comprises apercentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.The energy delivery zone can comprise less than 50% of the duodenalinner surface area if the patient has an HgBA1c level less than 9, suchas when a portion of the energy delivery zone receives energy from thetissue treatment element, and the portion receiving energy comprises apercentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.The energy delivery zone can comprise less than 75% of the duodenalinner surface area if the patient has an HgBA1c level less than 10, suchas when a portion of the energy delivery zone receives energy from thetissue treatment element, and the portion receiving energy comprises apercentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.The energy delivery zone can comprise less than 75% of the duodenalinner surface area if the patient has an HgBA1c level less than 12, suchas when a portion of the energy delivery zone receives energy from thetissue treatment element, and the portion receiving energy comprises apercentage of the energy delivery zone selected from the groupconsisting of: at least 2%; at least 5%; at least 10%; or at least 20%.

In some embodiments, the energy delivery zone and/or the target tissueto be treated is based on a patient characteristic selected from thegroup consisting of: duration of diabetes; HbA1c; area under the curveof a glucose tolerance test; area under the curve of a mixed mealtolerance test; C-peptide level; GIP level; GLP-1 level; age; BMI; andcombinations thereof.

In some embodiments, the energy delivery zone and/or the target tissueto be treated is based on a target diabetes endpoint result selectedfrom the group consisting of: target HbA1c level; target BMI; targetarea under the curve of glucose tolerance test; target cholesterollevel; target triglyceride level; and combinations thereof.

In some embodiments, the energy delivery zone comprises an anatomicallocation selected from the group consisting of: inner surface portion ofstomach; full circumferential inner surface of an axial segment ofduodenum; partial circumferential inner surface of an axial segment ofduodenum; full circumferential inner surface of an axial segment ofjejunum; partial circumferential inner surface of an axial segment ofjejunum; and combinations thereof.

In some embodiments, the energy delivery zone comprises an inner surfaceof at least one axial segment of the duodenum. The energy delivery zonecan comprise an inner surface of multiple axial segments of the duodenumand/or the jejunum. The energy delivery zone can comprise a relativelyfull circumferential segment of duodenal tissue. The at least one axialsegment can comprise a partial circumferential segment of duodenaltissue, such as when the partial circumferential segment comprises acircumferential segment between 45° and 350°. The target tissue cancomprise duodenal mucosal tissue. The target tissue can comprise tissueselected from the group consisting of: duodenal mucosal tissue; jejunalmucosal tissue; ileal mucosal tissue; gastric mucosal tissue; andcombinations thereof. The at least one axial segment can comprise aproximal end and a distal end. The proximal end can be located distal tobut within 5 cm of the ampulla of Vater, or within 2 cm of the ampullaof Vater. The proximal end can be located distal to but within 15 cm ofthe pylorus, such as within 10 cm of the pylorus. The proximal end canbe located distal to the duodenal bulb. The proximal end can be locatedproximate the most proximal location of the duodenum that includesplicae circulares. The proximal end can be located within 5 cm of theampulla of Vater and the distal end can be located proximal to theligament of Treitz. The distal end can be located at least 3 cm from theproximal end, such as at least 5 cm, at least 10 cm or at least 50 cmfrom the proximal end. The multiple axial segments can comprise multiplerelatively linear axial tissue segments, such as multiple relativelylinear full circumferential axial tissue segments.

In some embodiments, at least one axial segment of the duodenum is nottreated by the tissue treatment element. The at least one non-treatedaxial segment can comprise a segment of the duodenum absent of plicaecirculares. The at least one non-treated axial segment can comprise asegment of the duodenum containing the ampulla of Vater. The at leastone non-treated axial segment can comprise a curved segment of theduodenum with an approximate average radius of curvature less than 5 cmor less than 3 cm over a 75 degree arc, such as when the tissuetreatment element comprises a length with a maximum value of: 30 mm; 25mm; 20 mm; or 15 mm.

In some embodiments, the target tissue comprises one or more portions ofa tissue layer selected from the group consisting of: mucosa; mucosathrough superficial submucosa; mucosa through mid-submucosa; mucosathrough deep-submucosa; and combinations thereof.

In some embodiments, the target tissue and/or the energy delivery zonecomprises multiple tissue segments of the gastrointestinal tract. Themultiple tissue segments can be treated sequentially, such as withsequential treatments performed within a twenty-four hour period orwithin a six month period. The multiple tissue segments can be treatedsimultaneously. The multiple tissue segments can comprise between 2 and50 segments. At least two of the multiple tissue segments can comprisefull circumferential tissue segments. At least two of the multipletissue segments can comprise overlapping boundaries, such as when theenergy delivery zone comprises a first zone portion and a second zoneportion, and the first zone portion and the second zone portion compriseoverlapping boundaries. At least two of the multiple tissue segments cancomprise similar boundaries, such as when the energy delivery zonecomprises a first zone portion and a second zone portion, and the firstzone portion and the second zone portion comprise similar boundarysegments. The multiple tissue segments can be axially separated by lessthan or equal to 1 cm or less than or equal to 0.5 cm. The method canfurther comprise performing a tissue expansion procedure to an axialsegment of tissue, such as when the multiple tissue segments comprise aset of partial circumferential portions expanded during the tissueexpansion procedure. A first tissue segment receiving energy can beseparated from a second tissue segment receiving energy by a portion oftissue not receiving energy. A first partial circumferential expandedportion can be separated from a second partial circumferential expandedportion by a less expanded third partial circumferential expandedportion, where the target tissue treated comprises a greater thicknessat the first partial circumferential portion and the second partialcircumferential portion than the third partial circumferential portion.The multiple tissue segments can each comprise a length less than 20 cm,or less than 15 cm. The multiple tissue segments can comprise acumulative length less than 100 cm, or less than 50 cm.

In some embodiments, the method further comprises a step selected fromthe group consisting of: measuring tissue geometry; measuring targettissue geometry; expanding tissue; expanding target tissue; measuringapposition of a tissue treatment element; and combinations thereof.

In some embodiments, the method further comprises measuring targettissue geometry and expanding target tissue.

In some embodiments, the method further comprises measuring the diameterof tubular tissue with a sizing element.

In some embodiments, the method further comprises modifying the diameterof tubular tissue to modify energy delivery by the tissue treatmentelement, such as when the modification of energy delivery comprisesinitiating energy delivery; stopping energy delivery; increasing energydelivery and/or decreasing energy delivery.

In some embodiments, the method further comprises measuring theapposition of the tissue treatment element, such as when the method yetfurther comprises measuring target tissue geometry, and the measuring ofthe apposition of the tissue treatment element is based on the measuredtarget tissue geometry.

In some embodiments, the method further comprises measuring theimpedance between two or more electrodes, and using the measuredimpedance to measure tissue diameter and/or apposition of the tissuetreatment element.

In some embodiments, the target tissue treatment is based on acontrolled system parameter, such as when the controlled systemparameter comprises a parameter selected from the group consisting of: apriming procedure parameter such as priming temperature or primingduration; target tissue treatment parameter such as target tissuetemperature or target tissue treatment duration; fluid flow rate such astreatment fluid flow rate; a pressure parameter such as a tissuetreatment element pressure maintained during treatment of target tissue;a tissue treatment element diameter such as a tissue treatment elementdiameter maintained during treatment of target tissue; and combinationsthereof.

In some embodiments, the method further comprises controlling at leastone tissue treatment element parameter during the tissue treatment. Thetissue treatment element controlled parameter can comprise a parameterselected from the group consisting of: thermal dose delivered; primingtemperature; tissue treatment temperature; fluid flow rate; pumpingpressure; vacuum pressure; tissue treatment time; and combinationsthereof. The tissue treatment element can comprise a balloon and thetissue treatment element variable being controlled can comprise theballoon diameter. The method can further comprise selecting a balloondiameter prior to target tissue treatment.

In some embodiments, the target tissue is treated with an ablativeenergy treatment, such as an ablative energy treatment selected from thegroup consisting of: delivery of thermal energy from a balloon filledwith fluid at an ablative temperature; radiofrequency (RF) energyablation; delivery of an ablative fluid directly to tissue;cryoablation; delivery of laser energy; delivery of sound energy such assubsonic sound energy or ultrasonic sound energy; plasma energydelivery; argon plasma coagulation; microwave energy delivery; deliveryof non-laser light energy; and combinations thereof.

In some embodiments, the target tissue is treated with a non-ablativeenergy treatment, such as when the non-ablative treatment comprises atreatment selected from the group consisting of: mechanical removal ofmucosal tissue; chemical, sclerosant or pharmaceutical injection intothe submucosa; radioactive seed deposition; chemical spray such as anacid spray; pharmacologic administration such as drug delivery via anagent-eluting balloon; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to resect tissue. The tissue treatment element can beconstructed and arranged to resect tissue selected from the groupconsisting of: plicae tissue; mucosal tissue; submucosal tissue; andcombinations thereof. The tissue treatment element can be constructedand arranged to resect the plicae, such as a tissue treatment elementconstructed and arranged to resect peaks of the plicae including amajority of the proximate mucosal tissue.

In some embodiments, the target tissue is treated with multiple tissuetreatment steps. The multiple tissue treatment steps can comprisemultiple sequential deliveries of energy to tissue. The multiple tissuetreatment steps can comprise multiple sequential deliveries of ablativefluid to tissue. The multiple tissue treatment steps can comprisemultiple sequential abrasions of tissue. The method can further compriseexpanding one or more layers of tissue. The method can further compriseperforming two or more expansions of one or more layers of tissue.

In some embodiments, the target tissue comprises multiple tissuesegments with an inward facing surface, and the energy delivery zonecomprises between 50 and 3000 target tissue inward facing surfaces persquare centimeter of tissue. The energy delivery zone can compriseapproximately 500 target tissue segment inward facing surfaces persquare centimeter of tissue. The target tissue segment inward facingsurfaces can each comprise an equivalent diameter between approximately20 and 200 microns. The target tissue segment inward facing surfaces caneach comprise a surface area with a major axis less than or equal to 100microns. The energy can be delivered to the target tissue segment inwardfacing surfaces sequentially, such as when the energy is delivered witha scanning tissue treatment element, such as a scanning tissue treatmentelement constructed and arranged to rotate and translate, and thetranslation is between 0.5 cm and 3 cm in length. Alternatively oradditionally, the energy can be delivered to multiple target tissuesegment inward facing surfaces simultaneously. The tissue treatmentelement can comprise an element constructed and arranged to delivermultiple rays of ablative light energy, such as when the tissuetreatment element comprises a light delivery element and a shroud, andthe shroud comprises an opaque substrate with multiple transmissiveportions, such as when the shroud comprises an expandable element.Non-target tissue can be positioned between each of the target tissuesegment inward facing surfaces. The ratio of the surface area of thetarget tissue segment inward facing surfaces to the surface area of thenon-target tissue positioned between the inward facing surfaces can bebetween 0.1% and 90%. The ratio of the surface area of the target tissuesegment inward facing surfaces to the surface area of the non-targettissue positioned between the inward facing surfaces can be less than50%, less than 20%, less than 10%, less than 5%, less than 2% or lessthan 1%. A fractional energy delivery can be delivered to an axialsegment of gastrointestinal tissue in multiple passes. The target tissuesegment inward facing surfaces can each comprise relatively ellipticalcross sections, such as relatively circular cross sections. The targettissue segment inward facing surfaces can be treated at a temperature ator above 60° C., such as a temperature at or above 100° C., or at atemperature between 60° C. and 80° C. The target tissue segment inwardfacing surfaces can be vaporized. The target tissue segment inwardfacing surfaces can receive an energy type selected from the groupconsisting of: RF; ultrasound; laser light; non-laser light such asnon-laser light from an LED; chemical; and combinations thereof. Thetissue treatment element can deliver light energy from a laser. Thelight energy can be delivered through at least one fiber, such asthrough a coherent or non-coherent bundle of fibers. The light energycan be delivered to a balloon positioned in the gastrointestinal tract.The balloon can surround a volume of light-scattering material, such aslight-scattering material comprising material selected from the groupconsisting of: reflective polystyrene particles; aluminum flakes;reflective microspheres; and combinations thereof. The balloon cancomprise multiple apertures, such as an array of apertures in asymmetric or non-symmetric pattern, each aperture relatively transparentto the treatment element light energy being delivered. The laser cancomprise a laser selected from the group consisting of: CO2; Erbium;fiber laser; solid state crystal laser such as a Ho:YAG laser;semiconductor laser; and combinations thereof. The laser can deliverlight with a wavelength selected from the group consisting of: 2.0 to2.2 micron; 1.8 to 2.0 micron; 1.24 to 1.64 micron; and combinationsthereof. The laser can deliver light with a wavelength of 1.9 micronwavelength and/or 2.1 micron wavelength. The light energy can bedistributed by an array of lenses, such as an array comprising two ormore lenses selected from the group consisting of: holographic; fresnel;and combinations thereof. The tissue treatment element can comprise anenergy distribution element, such as an energy distribution elementcomprising an element selected from the group consisting of: rotatingelement such as a rotating mirror; prism; diffractive optic; andcombinations thereof. The energy delivery zone can comprise an areabetween 1.0 cm² and 5.0 cm². The method can further comprise expandingone or more layers of tissue. The one or more layers of tissue can beexpanded by injection of a non-energy absorbing material into tissue.The one or more layers of tissue can be expanded by injection of anenergy absorbing material into tissue, such as water or saline. Thetissue treatment element can comprise multiple electrodes constructedand arranged to deliver radiofrequency energy. The multiple electrodescan comprise multiple conductive dots positioned on an expandableballoon. The multiple electrodes can be constructed and arranged todeliver monopolar and/or bipolar radiofrequency energy. The multipleelectrodes can comprise an array of electrodes positioned on anexpandable element.

In some embodiments, the surface area reduction occurs at least one dayafter the target tissue treatment.

In some embodiments, the target tissue treatment causes a reduction in agastrointestinal tissue characteristic selected from the groupconsisting of: average height of mucosal folds; surface area of mucosalfolds; number of mucosal folds; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to reshape mucosal tissue. The tissue treatment element can beconstructed and arranged to flatten mucosal tissue. The tissue treatmentelement can be constructed and arranged to cause mucosal tissue toreshape at least 7 days after the tissue treatment is performed. Thetissue treatment element can be constructed and arranged to causemucosal tissue to reshape within 1 day of tissue treatment, such as whenthe tissue treatment element is constructed and arranged to deliverlight energy and/or RF energy.

In some embodiments, the target tissue treatment causes a reduction inaverage villi length.

In some embodiments, the target tissue treatment causes a reduction inthe quantity of villi.

In some embodiments, the tissue treatment element is constructed andarranged to reshape submucosal tissue. The reshaped submucosal tissuecan cause a healing response that results in a reduced amount of mucosaltissue. The reshaped submucosal tissue can comprise flattened submucosaltissue. The reshaped submucosal tissue can comprise submucosal tissuewith increased uniformity of thickness. The reshaped submucosal tissuecomprises submucosal tissue with increased averaged minimum thickness.The reshaped submucosal tissue comprises a reduced volume of submucosaltissue. The tissue treatment element can be constructed and arranged todeliver controlled thermal heating of the submucosal tissue, such aswhen the controlled thermal heating causes collagen of the submucosaltissue to shrink and/or become denatured. The tissue treatment elementcan be constructed and arranged to cause submucosal tissue to reshape atleast 7 days after the target tissue treatment is performed.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the volume of submucosal tissue.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the amount of submucosal tissue on which mucosaltissue grows.

In some embodiments, the target tissue treatment results in a smoothertissue surface in the at least a portion of the gastrointestinal tract.

In some embodiments, the target tissue treatment causes a reduction inthe quantity of plicae circulares in the at least a portion of thegastrointestinal tract.

In some embodiments, the target tissue treatment causes a reduction insurface area of absorptive tissue in the at least a portion of thegastrointestinal tract.

In some embodiments, the target tissue treatment treats stem cells. Thetreated stem cells can comprise mucosal stem cells and/or epithelialstem cells. The target tissue treatment can remove and/or ablate stemcells.

In some embodiments, the target tissue treatment causes a reduction inthe number of enteroendocrine cells in the at least a portion of thegastrointestinal tract.

In some embodiments, the target tissue treatment causes a reduction inthe number of absorptive cells in the at least a portion of thegastrointestinal tract.

In some embodiments, the surface area reduction occurs at least 7 daysafter the target tissue treatment is performed. The surface areareduction can further occur within 7 days of the target tissuetreatment. The surface area of the at least a portion of thegastrointestinal tract can be reduced at least 3 weeks after the targettissue treatment is performed, such as when the surface area of the atleast a portion of the gastrointestinal tract is reduced at least 6weeks after the target tissue treatment is performed.

In some embodiments, the method provides a therapeutic benefit for atleast 6 weeks, at least 6 months or at least 2 years. The method can berepeated after a duration of time of at least 6 weeks to reduce thesurface area of the gastrointestinal tract.

In some embodiments, the surface area reduced comprises the surface areaof the duodenum and/or the jejunum. The surface area of the duodenumand/or the jejunum can be reduced at least 5%, at least 10%, at least20%, at least 50%, or at least 90%.

In some embodiments, the method further comprises selecting one tissuetreatment element of a kit of tissue treatment elements prior totreating the target tissue.

In some embodiments, the method further comprises selecting and/orcontrolling the tissue treatment element size. The selecting orcontrolling the tissue treatment element size can comprise selecting atissue treatment element between 10 mm and 40 mm in diameter and/orcontrolling a tissue treatment element to a diameter between 10 mm and40 mm. The selecting or controlling the tissue treatment element sizecan comprise selecting a tissue treatment element between 15 mm and 32mm in diameter and/or controlling a tissue treatment element to adiameter between 15 mm and 32 mm.

In some embodiments, the method further comprises deflecting the tissuetreatment element prior to treating the target tissue.

In some embodiments, the method further comprises rotating the tissuetreatment element, such as when the tissue treatment element is rotatedprior to and/or during target tissue treatment by the tissue treatmentelement.

In some embodiments, the tissue treatment element comprises a radiallyexpandable element. The radially expandable element can be constructedand arranged to expand to a diameter between 15 mm and 32 mm, to as toexpand to a diameter between 19.0 mm and 27.5 mm. The radiallyexpandable element can comprise an element selected from the groupconsisting of: balloon; expandable cage; radially deployable arm; andcombinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to ablate tissue.

In some embodiments, the tissue treatment element is constructed andarranged to vaporize tissue.

In some embodiments, tissue treatment element is constructed andarranged to cause coagulation necrosis.

In some embodiments, the tissue treatment element comprises an energydelivery element. The tissue treatment element can comprise a balloonconstructed and arranged to receive a hot fluid. The hot fluid can beinitially provided to the balloon at a temperature greater than or equalto 90° C., and during the course of treating the target tissue, thetemperature allowed to decrease, such as to a temperature greater than70° C. The balloon can be constructed and arranged to receive a fixedvolume bolus of fluid. The balloon can be constructed and arranged toreceive a recirculating fluid. A cooling fluid can be delivered to theballoon, such as to cool target tissue and/or tissue proximate targettissue. The energy delivery element can comprise an RF energy deliveryelement, such as when the tissue treatment element comprises anexpandable element. The energy delivery element can comprise an elementselected from the group consisting of: laser; RF; ultrasound; andcombinations thereof.

In some embodiments, the tissue treatment element comprises a tissuecutting element. The tissue treatment element can be constructed andarranged to cut tissue during advancement and/or retraction of thetissue cutting element. Alternatively or additionally, the tissuetreatment element can comprise a tissue grasping element. The targettissue treatment can comprise grasping tissue and subsequently cuttingtissue.

In some embodiments, the tissue treatment element is positioned on thedistal portion of an elongate shaft. The elongate shaft can comprise adistal end with a bulbous element positioned on the distal end. Thebulbous element can comprise a diameter of less than 6 mm or less than 4mm. The bulbous element can comprise a diameter of at least 8 mm. Thebulbous element can be constructed and arranged to smoothly traverseplicae. The method can further comprise placing an endoscope into thegastrointestinal tract. The method can further comprise placing theelongate shaft through the endoscope and/or alongside the endoscope. Theelongate shaft can be constructed and arranged to be advanced over aguidewire.

In some embodiments, the method further comprises applying an algorithmto determine a treatment parameter. The algorithm can be constructed andarranged to determine an energy delivery zone parameter. The energydelivery zone parameter can comprise a parameter selected from the groupconsisting of: anatomical location of an energy delivery zone; size(e.g. surface area) of energy delivery zone; percentage of an energydelivery zone to receive energy; type of energy to be delivered to anenergy delivery zone; amount of energy to be delivered to an energydelivery zone; and combinations thereof. The algorithm can beconstructed and arranged to define the completion status of the clinicalprocedure. The algorithm can employ patient clinical data and/or patientdemographic data.

In some embodiments, the method further comprises identifying theampulla of Vater. The tissue treatment element can treat target tissuedistal to but in close proximity to the ampulla of Vater. The tissuetreatment element can treat target tissue proximal to but in closeproximity to the ampulla of Vater.

In some embodiments, the method further comprises expanding one or moretissue layers with a tissue expansion element. The expansion of one ormore layers of tissue can be performed prior to the target tissuetreatment. The at least one tissue layer can comprise a layer ofsubmucosal tissue. The expansion of one or more layers of tissue can beconstructed and arranged to flatten plicae circulares tissue. The tissueexpansion element can comprise a fluid delivery element constructed andarranged to deliver fluid into the one or more tissue layer to beexpanded, such as when the fluid delivery element comprises an elementselected from the group consisting of: needle; water jet; iontophoreticfluid delivery element; and combinations thereof. The fluid deliveryassembly can deliver a bolus of fluid to one or more tissue sites toexpand the one or more layers of tissue. The bolus of fluid can comprisea bolus of at least 1 ml, or a bolus of fluid between 2 ml and 5 ml. Thetissue expansion element can be constructed and arranged to deliverfluid to multiple tissue injection sites. The tissue expansion elementcan be constructed and arranged to deliver fluid to threecircumferential tissue injection sites along a single axial location oftubular tissue. A first tissue injection site can be approximately 1 cmfrom a second tissue injection site. A first tissue injection site canbe between 0.5 cm and 5.0 cm from a second tissue injection site. Afirst tissue injection site can be between 1.0 cm and 3.0 cm from asecond injection tissue site. A first tissue injection site can bebetween 1.0 cm and 2.0 cm from a second tissue injection site. Themultiple tissue injection sites can be axially spaced and/or radiallyspaced locations. The multiple tissue injection sites can be located intubular tissue, and the axial spacing and/or radial spacing is based onthe diameter of the tubular tissue. The tissue expansion element cancomprise a vacuum port constructed and arranged to apply a vacuum totissue. The material injected to expand tissue can comprise a materialselected from the group consisting of: water; saline; gel such as aprotein hydrogel; and combinations thereof. The tissue expansion elementcan be constructed and arranged to expand one or more layers ofgastrointestinal tissue. The one or more layers of tissue to be expandedcan comprise one or more duodenal tissue layers. The one or more layersof tissue to be expanded can comprise one or more jejunal tissue layers.The one or more layers of tissue to be expanded can comprise asubmucosal tissue layer. The target tissue treatment can be performed atleast 1 minute after the expansion of the one or more layers of tissue,or at least 5 minutes after the expansion of the one or more layers oftissue. The tissue treatment can be performed less than 20 minutes afterthe expansion of the one or more layers of tissue. The one or morelayers of expanded tissue can comprise an inner layer of an axialsegment of the duodenum and/or jejunum, while the energy delivery zonecomprises multiple, discontinuous partial circumferential portions ofthe axial segment. In some embodiments, energy is not delivered to atleast one partial circumferential tissue portion between two of thetreated portions of the axial segment.

In some embodiments, the method further comprises visualizing tissuewith a visualization element. The target tissue can be treated based onthe tissue visualization. The visualization element can comprise avisible light camera.

In some embodiments, the method further comprises protecting tissue witha tissue protection element. The protected tissue can comprise theampulla of Vater. The tissue protection element can be deployed before asegment of target tissue is treated. The tissue protection element canbe deployed before any target tissue is treated. The tissue protectionelement can be removed during the treatment of the target tissue. Thetissue protection element can be constructed and arranged to beevacuated by the patient's gastrointestinal system.

In some embodiments, the method further comprises protecting tissue witha thermal barrier and/or a thermal spacer.

In some embodiments, the tissue treatment element is advanced through abody lumen over a guidewire.

In some embodiments, the tissue treatment element is advanced through aworking channel of an endoscope.

According to another aspect of the present inventive concepts, a systemfor treating a patient comprises an elongate shaft with a distal portionand a tissue treatment element positioned on the elongate shaft. Thetissue treatment element is constructed and arranged to deliver energyto target tissue positioned in one or more energy delivery zones. Thesystem is constructed and arranged to reduce the luminal surface area ofat least a portion of the gastrointestinal tract.

In some embodiments, the surface area reduction comprises a reduction inmucosal surface area.

In some embodiments, the surface area reduction is constructed andarranged to reduce absorption and/or secretion of the at least a portionof the gastrointestinal tract.

In some embodiments, the system is constructed and arranged to treatdiabetes.

In some embodiments, the system is constructed and arranged to avoiddamage to non-target tissue, such as non-target tissue comprising theampulla of Vater.

In some embodiments, at least one energy delivery zone comprises aninner surface of an axial segment of the duodenum. The at least oneenergy delivery zone can comprise multiple energy delivery zones eachcomprising an inner surface of an axial segment positioned in theduodenum and/or the jejunum. The at least one energy delivery zone cancomprise a relatively full circumferential segment of duodenal tissue.The at least one energy delivery zone can comprise a partialcircumferential segment of duodenal tissue, such as a partialcircumferential segment comprising a circumferential segment between 45°and 350°. The target tissue can comprise duodenal mucosal tissue. Thetarget tissue can comprise tissue selected from the group consisting of:duodenal mucosal tissue; jejunal mucosal tissue; ileal mucosal tissue;gastric mucosal tissue; and combinations thereof.

In some embodiments, the target tissue and/or the energy delivery zonecomprises multiple tissue segments of the gastrointestinal tract. Themultiple tissue segments can comprise between 2 and 50 segments. Atleast two of the multiple tissue segments can comprise fullcircumferential tissue segments. At least two of the multiple tissuesegments can comprise overlapping boundaries, such as when the energydelivery zone comprises a first zone portion and a second zone portion,and the first zone portion and the second zone portion compriseoverlapping boundaries. At least two of the multiple tissue segments cancomprise similar boundaries, such as when the energy delivery zonecomprises a first zone portion and a second zone portion, and the firstzone portion and the second zone portion comprise similar boundarysegments. The multiple tissue segments can be axially separated by lessthan or equal to 1 cm, or less than or equal to 0.5 cm. The system canbe further constructed and arranged to perform a tissue expansionprocedure to an axial segment of tissue, and the multiple tissuesegments comprise a set of partial circumferential portions expandedduring the tissue expansion procedure. A first tissue segment receivingenergy can be separated from a second tissue segment receiving energy bya portion of tissue not receiving energy. A first partialcircumferential expanded portion can be separated from a second partialcircumferential expanded portion by a less expanded third partialcircumferential expanded portion, and the treated target tissue cancomprise a greater thickness at the first partial circumferentialportion and the second partial circumferential portion than the thirdpartial circumferential portion. The multiple tissue segments can eachcomprise a length less than 20 cm, such as a length less than 15 cm. Themultiple tissue segments can comprise a cumulative length less than 100cm, such as a cumulative length less than 50 cm.

In some embodiments, the tissue treatment element is constructed andarranged to deliver energy selected from the group consisting of: RFenergy; microwave energy; laser energy; sound energy such as subsonicsound energy or ultrasound energy; chemical energy; thermal energy suchas heat energy or cryogenic energy; mechanical energy; energy configuredto cut tissue; energy configured to resect tissue; and combinationsthereof.

In some embodiments, the tissue treatment element is constructed andarranged to perform an ablative treatment of target tissue, such as whenthe ablative treatment comprises a treatment selected from the groupconsisting of: delivery of thermal energy from a balloon filled withfluid at an ablative temperature; RF energy ablation; delivery of anablative fluid directly to tissue; cryoablation; delivery of laserenergy; delivery of sound energy such as subsonic sound energy orultrasonic sound energy; plasma energy delivery; argon plasmacoagulation; microwave energy delivery; delivery of non-laser lightenergy; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to perform a non-ablative treatment of target tissue, such aswhen the non-ablative treatment comprises a treatment selected from thegroup consisting of: mechanical removal of mucosal tissue; sclerosantinjection into the submucosa; radioactive seed deposition; chemicalspray such as an acid spray; pharmacologic administration such as drugdelivery via an agent-eluting balloon; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to resect tissue. The tissue treatment element can beconstructed and arranged to resect tissue selected from the groupconsisting of: plicae tissue; mucosal tissue; submucosal tissue; andcombinations thereof. The tissue treatment element can be constructedand arranged to resect plicae.

In some embodiments, the system is constructed and arranged to treattarget tissue with multiple tissue treatment steps. The multiple tissuetreatment steps can comprise multiple sequential deliveries of energy totissue. The multiple tissue treatment steps can comprise multiplesequential deliveries of ablative fluid to tissue. The multiple tissuetreatment steps can comprise multiple sequential abrasions of tissue.

In some embodiments, the system is constructed and arranged to treattarget tissue comprising multiple tissue segments with an inward facingsurface, such as when the energy delivery zone comprises between 50 and3000 target tissue inward facing surfaces per square centimeter oftissue. The energy delivery zone can comprise approximately 500 targettissue segment inward facing surfaces per square centimeter of tissue.The target tissue segment inward facing surfaces can each comprise anequivalent diameter between approximately 20 and 200 microns. The targettissue segment inward facing surfaces can each comprise a surface areawith a major axis less than or equal to 100 microns. The tissuetreatment element can be constructed and arranged to deliver energy tothe target tissue segment inward facing surfaces sequentially.Sequential energy delivery can be performed when the tissue treatmentelement comprises a scanning tissue treatment element, such as when thescanning tissue treatment element is constructed and arranged to rotateand translate, such as a translation between 0.5 cm and 3 cm in length.Alternatively or additionally, the tissue treatment element can beconstructed and arranged to deliver energy to multiple target tissuesegment inward facing surfaces simultaneously. The tissue treatmentelement can comprise an element constructed and arranged to delivermultiple rays of ablative light energy, such as when the tissuetreatment element comprises a light delivery element and a shroud, andthe shroud comprises an opaque substrate with multiple transmissiveportions (e.g. apertures). The shroud can comprise an expandableelement, such as a balloon with one or more apertures. The system can beconstructed and arranged to avoid damage to non-target tissue positionedbetween each of the target tissue segment inward facing surfaces. Theratio of the surface area of the target tissue segment inward facingsurfaces to the surface area of the non-target tissue positioned betweenthe inward facing surfaces (i.e. ratio of treated to non-treated surfaceareas) can be between 0.1% and 90%, such as a ratio of less than 50%,less than 20%, less than 10%, less than 5%, less than 2% or less than1%. The system can be constructed and arranged to perform a low-ratio or“fractional” energy delivery that is delivered to an axial segment ofgastrointestinal tissue in multiple passes. The tissue treatment elementcan be constructed and arranged to treat target tissue segment inwardfacing surfaces each comprising relatively elliptical cross sections,such as relatively circular cross sections. The tissue treatment elementcan be constructed and arranged to treat target tissue segment inwardfacing surfaces at a temperature at or above 60° C., such as at atemperature above 100° C. or at temperature between 60° C. and 80° C.The tissue treatment element can be constructed and arranged to vaporizethe target tissue segment inward facing surfaces. The tissue treatmentelement can be constructed and arranged to deliver energy to the targettissue segment inward facing surfaces with an energy selected from thegroup consisting of: RF; ultrasound; laser light; non-laser light suchas non-laser light from an LED; chemical; and combinations thereof. Thesystem can further comprise a laser, such as when the tissue treatmentelement is constructed and arranged to deliver light energy provided bythe laser. The system can further comprise at least one fiber (e.g. asingle fiber or a coherent or non-coherent bundle of fibers), and thelight energy can be delivered through the at least one fiber. The systemcan further comprise a balloon, and the light energy can be delivered toand/or from the balloon. The system can further compriselight-scattering material, and the balloon can be constructed andarranged to surround the light-scattering material, such aslight-scattering material selected from the group consisting of:reflective polystyrene particles; aluminum flakes; reflectivemicrospheres; and combinations thereof. The balloon can comprisemultiple apertures, such as an array of apertures in a symmetric ornon-symmetric pattern, each aperture relatively transparent to thetreatment element light energy being delivered to the target tissue. Thelaser can comprise a laser selected from the group consisting of: CO2;Erbium; fiber laser; solid state crystal laser such as a Ho:YAG laser;semiconductor laser; and combinations thereof. The laser can deliverlight with a wavelength selected from the group consisting of: 2.0 to2.2 micron; 1.8 to 2.0 micron; 1.24 to 1.64 micron; and combinationsthereof. The laser can deliver light with a wavelength of 1.9 micronwavelength and/or 2.1 micron wavelength. The system can be constructedand arranged to deliver light energy in an array of light beams. Thesystem can further comprise an array of lenses and/or other opticalcomponents, and the light energy can be distributed to target tissue bythe optical components, such as an array of lenses comprising two ormore lenses selected from the group consisting of: holographic; fresnel;and combinations thereof. The tissue treatment element can comprise anenergy distribution element, such as an energy distribution elementcomprising an element selected from the group consisting of: rotatingelement such as a rotating mirror; prism; diffractive optic; andcombinations thereof. The one or more energy delivery zones can eachcomprise an area between 1.0 cm² and 5.0 cm². The system can beconstructed and arranged to expand one or more layers of tissue. Thesystem can further comprise a non-energy absorbing material, and thesystem can be constructed and arranged to expand the one or more layersof tissue by injection of the non-energy absorbing material into tissue.The system can further comprise an energy absorbing material, and thesystem can be constructed and arranged to expand the one or more layersof tissue by injection of the energy absorbing material into tissue,such as when the energy absorbing material comprises water and/orsaline. The tissue treatment element can comprise multiple electrodesconstructed and arranged to deliver radiofrequency energy. The tissuetreatment element can comprise an expandable balloon and the multipleelectrodes can comprise multiple conductive dots positioned on theexpandable balloon. The multiple electrodes can be constructed andarranged to deliver monopolar and/or bipolar radiofrequency energy. Themultiple electrodes can comprise an array of electrodes positioned onany expandable element.

In some embodiments, the system further comprises a light source and thetissue treatment element comprises a balloon configured to deliver lightenergy received from the light source. The balloon can comprise multipleapertures such that the light energy passes through the multipleapertures. The system can further comprise light-scattering materialpositionable within the balloon and constructed and arranged to scatterthe light energy. The light source can comprise a laser light source.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in a gastrointestinal tissuecharacteristic selected from the group consisting of: the average heightof mucosal folds; surface area of mucosal folds; number of mucosalfolds; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to reshape mucosal tissue. The tissue treatment element can beconstructed and arranged to flatten mucosal tissue. The tissue treatmentelement can be constructed and arranged to cause mucosal tissue toreshape at least 7 days after the tissue treatment is performed. Thetissue treatment element can be constructed and arranged to causemucosal tissue to reshape within 1 day of tissue treatment, such as whenthe tissue treatment element is constructed and arranged to deliverlight energy and/or RF energy.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in average villi length.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in the quantity of villi.

In some embodiments, the tissue treatment element is constructed andarranged to reshape submucosal tissue. The tissue treatment element canbe constructed and arranged such that the reshaped submucosal tissuecauses a healing response resulting in a reduced amount of mucosaltissue. The reshaped submucosal tissue can comprise flattened submucosaltissue. The reshaped submucosal tissue can comprise submucosal tissuewith increased uniformity of thickness. The reshaped submucosal tissuecan comprise submucosal tissue with increased averaged minimumthickness. The tissue treatment element can be constructed and arrangedto deliver controlled thermal heating of the submucosal tissue, such aswhen the controlled thermal heating is constructed and arranged to causecollagen of the submucosal tissue to shrink and/or become denatured. Thetissue treatment element can be constructed and arranged to causesubmucosal tissue to reshape at least 7 days after the target tissuetreatment is performed.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the volume of submucosal tissue.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the amount of submucosal tissue on which mucosaltissue grows.

In some embodiments, the tissue treatment element is constructed andarranged to smooth the surface of the at least a portion of thegastrointestinal tract.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the quantity of plicae circulares in the at least aportion of the gastrointestinal tract.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in surface area of absorptive tissue inthe at least a portion of the gastrointestinal tract.

In some embodiments, the tissue treatment element is constructed andarranged to treat stem cells. The tissue treatment element can beconstructed and arranged to treat stem cells comprising mucosal stemcells and/or epithelial stem cells. The tissue treatment element can beconstructed and arranged to remove and/or ablate stem cells.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in the number of enteroendocrine cells inthe at least a portion of the gastrointestinal tract.

In some embodiments, the tissue treatment element is constructed andarranged to cause a reduction in the number of absorptive cells in theat least a portion of the gastrointestinal tract.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the surface area of the duodenum and/or the jejunum.The tissue treatment element can be constructed and arranged to reducethe surface area of the duodenum and/or the jejunum by at least 5%, atleast 10%, at least 20%, at least 50% or at least 90%.

In some embodiments, the tissue treatment element comprises at least anexpandable portion constructed and arranged to expand to a diameterbetween 10 and 40 mm. The tissue treatment element can comprise at leastan expandable portion constructed and arranged to expand to a diameterbetween 15 and 32 mm. The expandable portion comprises an elementselected from the group consisting of: balloon; expandable cage;radially deployable arm; and combinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to be radially deflected. The distal portion of the shaft canbe constructed and arranged to be radially deflected, such as when thetissue treatment element is positioned on the distal portion of theshaft.

In some embodiments, the tissue treatment element is constructed andarranged to be rotated and/or translated. The tissue treatment elementcan be constructed and arranged to be both rotated and translated.

In some embodiments, the tissue treatment element is constructed andarranged to ablate tissue.

In some embodiments, the tissue treatment element is constructed andarranged to vaporize tissue.

In some embodiments, the tissue treatment element is constructed andarranged to cause coagulation necrosis.

In some embodiments, the tissue treatment element comprises an energydelivery element. The tissue treatment element can comprises a balloonconstructed and arranged to receive a hot fluid. The hot fluid can beinitially provided to the balloon at a temperature greater than or equalto 90° C., and the temperature can decrease during the course oftreating the target tissue, such as a decrease to a temperature greaterthan 70° C. The balloon can be constructed and arranged to receive afixed volume bolus of fluid. The balloon can be constructed and arrangedto receive a recirculating fluid. A cooling fluid can be delivered tothe balloon, such as to cool target tissue and/or non-target tissueprior to or after target tissue treatment. The energy delivery elementcan comprise an RF energy delivery element, such as an expandable RFenergy delivery element. The energy delivery element can comprise anelement selected from the group consisting of: laser; RF; ultrasound;and combinations thereof.

In some embodiments, the tissue treatment element comprises a tissuecutting element. The tissue treatment element can be constructed andarranged to cut tissue during advancement and/or retraction of thetissue cutting element. Alternatively or additionally, the tissuetreatment element can comprise a tissue grasping element. The tissuetreatment element can be constructed and arranged to grasp and/or cuttissue.

In some embodiments, the tissue treatment element is constructed andarranged to deliver energy to less than 100% (of the surface area) ofeach of the multiple energy delivery zones. The tissue treatment elementcan be constructed and arranged to deliver energy to less than 50% ofeach of the multiple energy delivery zones, or less than 20%, or lessthan 10%, or less than 5%, or less than 2% or less than 1% of each ofthe multiple energy delivery zones.

In some embodiments, the tissue treatment element is constructed andarranged to perform a fractional energy delivery of energy to targettissue.

In some embodiments, the tissue treatment element is positioned on thedistal portion of the shaft.

In some embodiments, the tissue treatment element comprises anexpandable tissue treatment element.

In some embodiments, the system is constructed and arranged to determineapposition of the tissue treatment element against tissue.

In some embodiments, the shaft is constructed and arranged to beinserted into the patient. The system may further comprise a guidewire,and the shaft can be constructed and arranged to be inserted into thepatient over the guidewire. The shaft can be constructed and arranged tobe inserted thru an endoscope and/or alongside an endoscope.

In some embodiments, the shaft comprises a distal end with a bulbouselement positioned on the distal end. The bulbous element can comprise adiameter of less than 6 mm or less than 4 mm. The bulbous element cancomprise a diameter of at least 8 mm. The bulbous element can beconstructed and arranged to smoothly traverse plicae.

In some embodiments, the system further comprises a handle positioned onthe proximal end of the shaft. The handle can comprise at least onefluid port constructed and arranged to deliver ablative fluid to thetissue treatment element.

In some embodiments, the system further comprises an endoscope.

In some embodiments, the system further comprises a sizing deviceconstructed and arranged to perform a tissue measurement procedure. Thesizing element can comprise an expandable element constructed andarranged to expand to measure diameter of tubular tissue. The expandableelement can comprise an element selected from the group consisting of:balloon; expandable cage; and combinations thereof. The sizing elementcan be positioned on the shaft. The system can further comprise a secondelongate shaft, and the sizing element can be positioned on the secondshaft. The tissue treatment element can comprise the sizing element.

In some embodiments, the system further comprises a tissue expansionelement constructed and arranged to expand one or more layers of tissue.The tissue expansion element can comprise a fluid delivery elementselected from the group consisting of: needle; water jet; iontophoreticfluid delivery element; and combinations thereof. The tissue expansionelement can be positioned on the shaft. The system can further comprisea second elongate shaft, and the tissue expansion element can bepositioned on the second elongate shaft. The tissue expansion elementcan be constructed and arranged to flatten plicae circulares tissue. Thesystem can further comprise a fluid delivery assembly and a fluid bolus,and the fluid delivery assembly can be constructed and arranged todeliver the bolus of fluid to one or more tissue sites to expand the oneor more layers of tissue. The bolus of fluid can comprise a bolus of atleast 1 ml, such as a bolus of fluid between 2 ml and 5 ml. The fluidbolus can comprise an injectable material selected from the groupconsisting of: water; saline; gel; and combinations thereof. The fluidbolus can comprise a protein hydrogel. The tissue expansion element canbe constructed and arranged to deliver fluid to multiple tissueinjection sites. The tissue expansion element can be constructed andarranged to deliver fluid to three circumferential tissue injectionsites along a single axial location of tubular tissue. The multipletissue injection sites can be approximately 1 cm apart, or between 0.5cm to 5 cm apart, such as between 1 cm and 3 cm apart, or between 1 cmand 2 cm apart. The multiple tissue injection sites can be axiallyspaced and/or radially spaced. The multiple tissue injection sites canbe located in tubular tissue, and the axial spacing and/or radialspacing can be based on the diameter of the tubular tissue. The tissueexpansion element can comprise a vacuum port constructed and arranged toapply a vacuum to tissue.

In some embodiments, the system further comprises a tissue protectionelement. The tissue protection element can be constructed and arrangedto protect the ampulla of Vater. The tissue protection element can beconstructed and arranged to be deployed before a segment of targettissue is treated. The tissue protection element can be constructed andarranged to be deployed before any target tissue is treated. The tissueprotection element can be constructed and arranged to be removed duringthe treatment of the target tissue. The tissue protection element can beconstructed and arranged to be evacuated by the patient'sgastrointestinal system. The tissue protection element can comprise athermal barrier and/or a thermal spacer.

In some embodiments, the system further comprises a second tissuetreatment element. The system can further comprise a second elongateshaft, and the second tissue treatment element can be positioned on thesecond shaft.

In some embodiments, the system further comprises a visualizationelement. The visualization element can comprise a visible light camera.

In some embodiments, the system further comprises an imaging agent.

In some embodiments, the system further comprises a controllerconstructed and arranged to control and/or monitor a system parameter.The system parameter can be selected from the group consisting of: apriming procedure parameter such as priming temperature or primingduration; target tissue treatment parameter such as target tissuetemperature or target tissue treatment duration; fluid flow rate such astreatment fluid flow rate; a pressure parameter such as a tissuetreatment element pressure maintained during treatment of target tissue;a tissue treatment element diameter such as a tissue treatment elementdiameter maintained during treatment of target tissue; and combinationsthereof. The system parameter can comprise a tissue treatment elementparameter, such as a parameter selected from the group consisting of:thermal dose delivered; priming temperature; tissue treatmenttemperature; fluid flow rate; pumping pressure; vacuum pressure; tissuetreatment time; and combinations thereof. The system can furthercomprise a balloon, and the controller can be constructed and arrangedto control the diameter of the balloon.

In some embodiments, the system further comprises an algorithm. Thealgorithm can be constructed and arranged to determine an energydelivery zone parameter, such as an energy delivery zone parameterselected from the group consisting of: anatomical location of an energydelivery zone; size of energy delivery zone; percentage of energydelivery zone to receive energy; type of energy to be delivered to anenergy delivery zone; amount of energy to be delivered to an energydelivery zone; and combinations thereof. The algorithm can beconstructed and arranged to determine the completion status of theclinical procedure. The algorithm can employ patient clinical dataand/or patient demographic data.

In some embodiments, the system further comprises a motion transferassembly operably attached to the tissue treatment element. The motiontransfer assembly can be constructed and arranged to rotate and/ortranslate the tissue treatment element, such as when the motion transferassembly is constructed and arranged to both rotate and translate thetissue treatment element. The motion transfer assembly can beconstructed and arranged to move the tissue treatment element in areciprocating motion.

In some embodiments, the system further comprises a pumping assemblyconstructed and arranged to deliver and/or remove fluid from the tissuetreatment element. The system can further comprise a fluid reservoirfluidly attached to the pumping assembly.

According to another aspect of the present inventive concepts, a devicefor delivering light energy to a patient comprises an elongate shaftwith a distal portion and a tissue treatment element positioned on theelongate shaft. The tissue treatment element is constructed and arrangedto deliver light energy to target tissue positioned in one or moreenergy delivery zones. The device is constructed and arranged to reducethe luminal surface are of at least a portion of the gastrointestinaltract.

In some embodiments, the device further comprises one or more fiberspositioned within the shaft, and the light energy can be configured topass through the one or more fibers (e.g. a single fiber or multiplefibers in a coherent or non-coherent bundle).

In some embodiments, the tissue treatment element is positioned on thedistal portion of the shaft.

In some embodiments, the tissue treatment element comprises a balloon.The device can further comprise light-scattering material, and theballoon can be constructed and arranged to surround the light-scatteringmaterial. The light-scattering material can comprise material selectedfrom the group consisting of: reflective polystyrene particles; aluminumflakes; reflective microspheres; and combinations thereof. The ballooncan comprise multiple apertures.

In some embodiments, the light energy is received from a light sourceoperably attached to the shaft. The device can further comprise a handleattached to the shaft, and the light source can be operably attached tothe handle.

In some embodiments, the light energy comprises laser light energy. Thelaser light energy can comprise light energy delivered from a laserselected from the group consisting of: CO2; Erbium; fiber laser; solidstate crystal laser such as a Ho:YAG laser; semiconductor laser; andcombinations thereof.

In some embodiments, the light energy comprises light with a wavelengthselected from the group consisting of: 2.0 to 2.2 micron; 1.8 to 2.0micron; 1.24 to 1.64 micron; and combinations thereof.

In some embodiments, the light energy comprises light with a wavelengthof 1.9 micron wavelength and/or 2.1 micron wavelength.

In some embodiments, the device is constructed and arranged to deliverlight energy in an array of light beams.

In some embodiments, the device further comprises an array of lenses,and the light energy can be distributed to target tissue by the array oflenses. The array of lenses can comprise two or more lenses selectedfrom the group consisting of: holographic; fresnel; and combinationsthereof.

In some embodiments, the tissue treatment element comprises a lightenergy distribution element. The light energy distribution element cancomprise an element selected from the group consisting of: rotatingelement such as a rotating mirror; prism; diffractive optic; andcombinations thereof.

In some embodiments, the tissue treatment element is constructed andarranged to reduce the surface area of the duodenum and/or the jejunum.The tissue treatment element can be constructed and arranged to reducethe surface area of the duodenum and/or the jejunum by at least 5%, orat least 10%, or at least 20%, or at least 50%, or at least 90%.

In some embodiments, the tissue treatment element is constructed andarranged to deliver light energy to less than 100% of each of themultiple energy delivery zones, such as to less than 50%, less than 20%,less than 10%, less than 5%, less than 2% or less than 1% of each of themultiple energy delivery zones.

In some embodiments, the tissue treatment element is constructed andarranged to perform a fractional energy delivery of light energy totarget tissue.

According to another aspect of the present inventive concepts, a methodfor treating a patient comprises providing a tissue treatment elementconstructed and arranged to deliver energy to tissue; and treatingtarget tissue of the patient by causing the tissue treatment element todeliver energy to an energy delivery zone. The method is constructed andarranged to cause a reduction in the surface area of at least a portionof a tissue surface of the patient.

In some embodiments, the method treats a disease or disorder selectedfrom the group consisting of: diabetes; pre-diabetes; impaired glucosetolerance; insulin resistance; obesity or otherwise being overweight;hypercholesterolemia; exercise intolerance; psoriasis; hypertension;hypertriglyceridemia; metabolic syndrome; and combinations thereof.

In some embodiments, the method treats at least a first patient diseaseor disorder and a second patient disease or disorder.

In some embodiments, the target tissue comprises tissue of the terminalileum and the method treats at least one of hypercholesterolemia ordiabetes, such as when the target tissue further comprises tissue of atleast the proximal ileum or the colon.

In some embodiments, the target tissue comprises gastric mucosal tissueand the method treats at least one of obesity or an appetite disorder.

In some embodiments, the target tissue comprises bladder wall tissue andthe method treats at least one of: interstitial cystitis; bladdercancer; bladder polyps; or pre-cancerous lesions of the bladder.

In some embodiments, the target tissue comprises tissue selected fromthe group consisting of: large colonic polyps; flat colonic polyps;margin tissue remaining after a polypectomy; and combinations thereof,and the method treats residual cancer cells.

In some embodiments, the target tissue comprises airway lining tissueand the method treats at least one of: bronchoalveolar carcinoma; otherlung cancers; or pre-cancerous lung lesions.

In some embodiments, the target tissue comprises a portion of theintestinal tract afflicted with inflammatory bowel disease and themethod treats at least one of Crohn's disease or ulcerative colitis.

In some embodiments, the target tissue comprises oral cavity tissue andthe method treats at least one of oral cancer or a pre-cancerous lesion.

In some embodiments, the target tissue comprises tissue of thenasopharynx and the method treats nasal polyps.

In some embodiments, the target tissue comprises gastrointestinal tissueand the method treats at least one of Celiac disease or intestinalbarrier function.

The technology described herein, along with the attributes and attendantadvantages thereof, will best be appreciated and understood in view ofthe following detailed description taken in conjunction with theaccompanying drawings in which representative embodiments are describedby way of example.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the technology described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the technology.

FIG. 1 is a flow chart of a method of treating target tissue in apatient, consistent with the present inventive concepts.

FIG. 1A is a perspective view of a tissue surface and an energy deliveryzone, consistent with the present inventive concepts.

FIG. 1B is a side sectional view of a portion of the energy treatmentzone of FIG. 1A, after energy has been delivered to target tissue;consistent with the present inventive concepts.

FIG. 1C is a perspective view of a tubular segment of gastrointestinaltissue including two energy delivery zones positioned in the lumen ofthe tubular segment, consistent with the present inventive concepts.

FIG. 1D is a side sectional view of a portion of the two energy deliveryzones of FIG. 1C, after a high surface area proportion energy deliveryhas been delivered to target tissue; consistent with the presentinventive concepts.

FIG. 1E is a side sectional view of a portion of a first energy deliveryzone of FIG. 1C, after a low surface area proportion energy delivery hasbeen delivered to target tissue; consistent with the present inventiveconcepts.

FIG. 2A is a photograph of a cross section of mammalian duodenal tissueprior to a target tissue treatment, consistent with the presentinventive concepts.

FIGS. 2B and 2C are photographs of cross sections of mammalian duodenaltissue subsequent to a target tissue treatment, consistent with thepresent inventive concepts.

FIG. 3 is a schematic view of a system for ablating or otherwisetreating target tissue, consistent with the present inventive concepts.

FIG. 4 is a side sectional view of the distal portion of a treatmentdevice inserted into a curvilinear section of duodenum, consistent withthe present inventive concepts.

FIGS. 5A and 5B are side and side sectional views of the distal portionof a light-energy delivering tissue treatment device, consistent withthe present inventive concepts.

FIG. 6 is a side sectional view of the distal portion of a treatmentdevice inserted into a curvilinear section of the GI tract, consistentwith the present inventive concepts.

FIGS. 7A, 7B and 7C are end sectional views of a tubular segment ofgastrointestinal tissue, prior to tissue expansion, after tissueexpansion and after target tissue treatment, respectively, consistentwith the present inventive concepts.

FIGS. 8A, 8B and 8C are end sectional views of a tubular segment ofgastrointestinal tissue prior to tissue expansion, after tissueexpansion and after target tissue treatment, respectively, consistentwith the present inventive concepts.

DETAILED DESCRIPTION OF THE INVENTION

Reference will now be made in detail to the present embodiments of theinventive concepts, examples of which are illustrated in theaccompanying drawings. Wherever practical, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

The terminology used herein is for the purpose of describing particularembodiments and is not intended to be limiting of the inventiveconcepts. As used herein, the singular forms “a,” “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise.

It will be further understood that the words “comprising” (and any formof comprising, such as “comprise” and “comprises”), “having” (and anyform of having, such as “have” and “has”), “including” (and any form ofincluding, such as “includes” and “include”) or “containing” (and anyform of containing, such as “contains” and “contain”) when used herein,specify the presence of stated features, integers, steps, operations,elements, and/or components, but do not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components, and/or groups thereof.

It will be understood that, although the terms first, second, third etc.may be used herein to describe various limitations, elements,components, regions, layers and/or sections, these limitations,elements, components, regions, layers and/or sections should not belimited by these terms. These terms are only used to distinguish onelimitation, element, component, region, layer or section from anotherlimitation, element, component, region, layer or section. Thus, a firstlimitation, element, component, region, layer or section discussed belowcould be termed a second limitation, element, component, region, layeror section without departing from the teachings of the presentapplication.

It will be further understood that when an element is referred to asbeing “on” or “connected” or “coupled” to another element, it can bedirectly on or above, or connected or coupled to, the other element orintervening elements can be present. In contrast, when an element isreferred to as being “directly on” or “directly connected” or “directlycoupled” to another element, there are no intervening elements present.Other words used to describe the relationship between elements should beinterpreted in a like fashion (e.g., “between” versus “directlybetween,” “adjacent” versus “directly adjacent,” etc.). When an elementis referred to herein as being “over” another element, it can be over orunder the other element, and either directly coupled to the otherelement, or intervening elements may be present, or the elements may bespaced apart by a void or gap.

The term “and/or” where used herein is to be taken as specificdisclosure of each of the two specified features or components with orwithout the other. For example “A and/or B” is to be taken as specificdisclosure of each of (i) A, (ii) B and (iii) A and B, just as if eachis set out individually herein.

As described herein, room pressure shall mean pressure of theenvironment surrounding the systems and devices of the present inventiveconcepts. Positive pressure includes pressure above room pressure or apressure that is greater than another pressure, such as a positivedifferential pressure across a fluid pathway component such as a valve.Negative pressure includes pressure below room pressure or a pressurethat is less than another pressure, such as a negative differentialpressure across a fluid component pathway such as a valve. Negativepressure can include a vacuum but does not imply a pressure below avacuum.

As used herein, the term “ablative fluid” refers to one or more fluidswhose chemical properties (at room temperature, body temperature orotherwise) cause tissue necrosis or another desired tissue treatment.“Ablative fluid” shall also refer to any fluid at a sufficiently high orlow temperature to cause a desired modification of tissue, such astissue ablation. The hot or cold ablative fluid can be delivereddirectly to a tissue surface to treat tissue, or it can be delivered toa reservoir such as a balloon configured to treat tissue via contact(e.g. add to or remove sufficient heat from the balloon contacted tissueto cause tissue necrosis).

It is an object of the present inventive concepts to provide systems,methods and devices for safely and effectively cutting, abrading,ablating, removing and/or otherwise treating a volume of tissue (the“target tissue”), such as to treat a patient disease or disorder. Targettissue can comprise one or more target tissue segments or other targettissue portions. The target tissue can comprise one or more layers of aportion of tubular or non-tubular tissue, such as tissue of an organ ortissue of the gastrointestinal (GI) tract of a patient. The systems anddevices of the present inventive concepts include one or more treatmentdevices configured to treat the target tissue, such as one or moredevices including one or more treatment assemblies. The treatmentassemblies can be configured to deliver energy to tissue, such as tocause a reduction in the surface area of tissue (e.g. the luminalsurface area of tubular tissue) at or proximate to where the energy wasdelivered. The luminal or other tissue surface area reduction can occuracutely and/or it can take place over time such as days, weeks ormonths. The tissue surface area reduction can correspond to a reductionin mucosal surface area available to function in an absorptive and/or asecretory capacity. The tissue surface area reduction can provide atherapeutic benefit to the patient, such as to treat one or morediseases or disorder of the patient, as described in detail herebelow.

Each treatment assembly can comprise at least one tissue treatmentelement such as a balloon configured to receive ablative fluid, one ormore electrodes configured to deliver RF energy, one or more lightdelivery elements configured to deliver laser or other light energy,and/or one or more fluid delivery elements configured to deliver anablative fluid directly to tissue. Numerous forms of treatmentassemblies and treatment elements can be included. In some embodiments,the treatment assemblies and/or the one or more treatment elementscontained therein are configured as described in: applicant'sco-pending, U.S. patent application Ser. No. 13/945,138, entitled“Devices and Methods for the Treatment of Tissue”, filed Jan. 18, 2013;applicant's co-pending International PCT Application Serial NumberPCT/US2013/28082, entitled “Heat Ablation Systems, Devices and Methodsfor the Treatment of Tissue”, filed Feb. 27, 2013; applicant'sco-pending International PCT Application Serial NumberPCT/US2013/052786, entitled “Electrical Energy Ablation Systems, Devicesand Methods for the Treatment of Tissue”, filed Jul. 30, 2013;applicant's co-pending International PCT Application Serial NumberPCT/US2013/054219, entitled “Ablation Systems, Devices and Methods forthe Treatment of Tissue”, filed Aug. 8, 2013; the contents of each ofwhich is incorporated herein by reference in its entirety.

The tissue treatment elements of the present inventive concepts candeliver energy to a particular area of tissue, the “energy deliveryzone”. During a single energy delivery, a treatment element can beconstructed and arranged to deliver energy to a relatively continuoussurface of tissue. In these continuous-surface energy deliveryembodiments, the energy delivery zone comprises the continuous surfaceof tissue. Alternatively, a treatment element can be constructed andarranged to deliver energy to multiple discrete portions of tissuesurface, with one or more tissue portions in-between that do not receiveenergy from the treatment element. In these segmented-surface energydelivery embodiments, the energy delivery zone is defined by a peripheryof the multiple tissue surface area portions receiving energy, similarto a “convex hull” or “convex envelope” used in mathematics to define anarea including a number of discrete locations that define a periphery.An energy delivery zone can comprise one or more energy delivery zones.

For example, in embodiments where the treatment element is a balloonfilled with hot fluid, the energy delivery zone comprises all tissuesurfaces contacted by the balloon that directly receive thermal energyfrom the balloon. In embodiments where the treatment element is an arrayof electrodes configured to deliver RF energy, the energy delivery zonecomprises an area defined by the electrodes on the periphery of thearray (e.g. a convex hull as described above). In embodiments where thetreatment element comprises one or more fluid delivery elementsdelivering ablative fluid to tissue, the energy delivery zone comprisesa surface defined by the periphery of tissue locations receiving theablative fluid. In embodiments where the treatment element comprises oneor more light delivery elements such as those that deliver laser energyto tissue, the energy delivery zone comprises a surface area defined bythe periphery of tissue locations receiving the light energy. Inembodiments in which the treatment element comprises a mechanicalcutter, the energy delivery zone can comprise a surface defined by alltissue dissected or otherwise cut during a single cutting step of themechanical cutter.

An energy delivery zone can comprise a cumulative set of energy deliveryzones that receive energy simultaneously or sequentially, by one or moretissue treatment elements, such as those described immediatelyhereabove. An energy delivery zone can comprise a first energy deliveryzone defined when a treatment element treats target tissue in a firstenergy delivery, plus a second energy delivery zone defined when thetreatment element treats target tissue in a second energy delivery, andso on. In these embodiments, the treatment element can be translated orotherwise repositioned between energy deliveries, and each energydelivery zone associated with the position of the treatment elementduring the delivery of energy. Multiple energy delivery zones canreceive energy in a single procedure, such as within a period of lessthan twenty-four hours. An energy delivery zone can comprise a similarcumulative set of multiple energy delivery zones delivered by two ormore treatment elements.

In some embodiments, two or more clinical procedures are performed inwhich one or more volumes of target tissue are treated in each clinicalprocedure, such as is described in applicant's co-pending InternationalPCT Application Serial Number PCT/US2013/063573, entitled “Methods,Systems and Devices for Performing Multiple Treatments on a Patient”,filed Oct. 7, 2013. For example, a second clinical procedure can beperformed at least twenty-four hours after the first clinical procedure,such as a second clinical procedure performed within six months of afirst clinical procedure or a clinical procedure performed after atleast 6 months from the first clinical procedure. The first and secondclinical procedures can be performed using similar or dissimilarmethods, and they can be performed using similar or dissimilar devices(e.g. performed with similar or dissimilar treatment elements). Thefirst and second clinical procedures can treat similar or dissimilarvolumes of target tissue (e.g. similar or dissimilar amounts of tissuetreated and/or locations of tissue treated), and they can deliver energyto similar or dissimilar sets of multiple energy delivery zones. In someembodiments, the first and second clinical procedures can includetreating and/or delivering energy to contiguous and/or overlappingregions of the GI tract either in the circumferential and/or axialdimensions. In other embodiments, the first and second clinicalprocedures can include the treatment of disparate regions of the GItract (such as disparate regions of the duodenum, ileum, and/orstomach). The first and second clinical procedures can be performedusing similar or dissimilar treatment devices. The first and secondclinical procedures can comprise similar or dissimilar deliveries ofenergy to treat the target tissue. The first and second clinicalprocedures can be performed at similar or dissimilar temperatures. Thesecond clinical procedure can be performed based on diagnostic resultscollected after the first clinical procedure has been performed.

Each treatment assembly of the present inventive concepts can beconfigured to treat target tissue in one or more locations of thepatient, such as one or more contiguous or discontiguous tissuelocations. The target tissue comprises a three dimensional volume oftissue, and can include a first portion, a treatment portion, whosetreatment has a therapeutic benefit to a patient; as well as a secondportion, a “safety-margin” portion, whose treatment has minimal or noadverse effects to the patient. “Non-target tissue” can be identified(e.g. prior to and/or during the medical procedure), wherein thenon-target tissue comprises tissue whose treatment by the treatmentassembly should be reduced or avoided such as to reduce or prevent anundesired effect.

The target tissue treatment can cause one or more effects to the targettissue such as an effect selected from the group consisting of:modification of cellular function; cell death; apoptosis; instant celldeath; cell necrosis; denaturing of cells; removal of cells; andcombinations of these. In some embodiments, the target tissue treatmentis configured to create scar tissue. Target tissue can be selected suchthat after treatment the treated target tissue and/or the tissue thatreplaces the target tissue functions differently than the pre-treatedtarget tissue, such as to have a therapeutic benefit. The modifiedand/or replacement tissue can have different secretions and/orquantities of secretions than the pre-treated target tissue, such as totreat diabetes and/or obesity. The modified and/or replacement tissuecan have different absorptive properties than the target tissue, such asto treat diabetes, obesity and/or hypercholesterolemia. The modifiedand/or replacement tissue can have a different surface topography thanthe target tissue, such as a modification of the topography of the innerwall of the GI tract that includes a smoothing or flattening of itsinner surface, such as a modification in which the luminal surface areaof one or more segments of GI tract is reduced after treatment. Theeffect of the treatment can occur acutely, such as within twenty-fourhours, or after longer periods of time such as greater than twenty-fourhours or greater than one week.

Target tissue to be treated can comprise two or more discrete tissuesegments, such as two or more axial segments of the GI tract. Eachtissue segment can comprise a full or partial circumferential segment ofthe tissue segment. Multiple tissue segments can be treated with thesame or different treatment elements, and they can be treatedsimultaneously or in sequential steps (e.g. sequential energy deliverysteps that deliver energy to multiple energy delivery zones). Multipletissue segments can be treated in the same or different clinicalprocedures (e.g. procedures performed on different days). In someembodiments, a series of tissue segments comprising a series of axialsegments of the GI tract are treated in a single clinical procedure. Thefirst and second tissue segments can be directly adjacent and they cancontain overlapping portions of tissue. Dissimilarities in treatmentelements can include type and/or amount of energy to be delivered by anenergy delivery based treatment assembly. Dissimilarities in targettissue treatments can include: target tissue area treated; target tissuevolume treated; target tissue length treated; target tissue depthtreated; target tissue circumferential portion treated; ablative fluidtype, volume and/or temperature delivered to a reservoir such as aballoon; ablative fluid type, volume and/or temperature delivereddirectly to tissue; energy delivery type; energy delivery rate and/oramount; peak energy delivered; average temperature of target tissueachieved during target tissue treatment; maximum temperature achievedduring target tissue treatment; temperature profile of target tissuetreatment; duration of target tissue treatment; surface area reductionachieved by target tissue treatment; and combinations of these.

Target tissue can include tissue of the duodenum, such as tissueincluding substantially all or a limited portion of the mucosal layer ofthe duodenum (e.g. including all or a portion of the plicae circulares),such as to treat diabetes and/or obesity while leaving the duodenumanatomically connected after treatment. Target tissue can include one ormore portions of a tissue layer selected from the group consisting of:mucosa; mucosa through superficial submucosa; mucosa throughmid-submucosa; mucosa through deep-submucosa; and combinations of these.Replacement tissue can comprise cells that have migrated from one ormore of: gastric mucosa; jejunal mucosa; an untreated portion of theduodenum whose mucosal tissue functions differently than the treatedmucosal tissue functions prior to treatment; and combinations of these.Replacement tissue can include one or more tissue types selected fromthe group consisting of: scar tissue; normal intestinal mucosa; gastricmucosa; and combinations of these. In some embodiments, target tissueincludes a treatment portion comprising the mucosal layer of theduodenum, and a safety-margin portion comprising a near-full or partiallayer of the submucosal layer of the duodenum. In some embodiments, thetarget tissue comprises nearly the entire mucosal layer of the duodenum,and can include a portion of the pylorus contiguous with the duodenalmucosa and/or a portion of the jejunum contiguous with the duodenalmucosa. In other embodiments, the target tissue comprises up to 50% orup to 75% of the mucosal layer, such as when up to 50% or up to 75%,respectively, of the length of the duodenum is treated by an tissuetreatment element delivering energy to full circumferential axialsegment of the duodenum.

Treatment of duodenal tissue can be performed to treat a disease and/ordisorder selected from the group consisting of: diabetes; pre-diabetes;impaired glucose tolerance; insulin resistance; obesity or otherwisebeing overweight; a metabolic disorder and/or disease; and combinationsof these. A near full circumferential portion (e.g. approximately) 360°of the mucosal layer of one or more axial segments of GI tissue can betreated. In some embodiments, less than 360° of one or more axialsegments of tubular tissue is treated, such as one or morecircumferential portions less than 350°, or between 300° and 350°, suchas to prevent a full circumferential scar from being created at the oneor more axial segment locations.

Target tissue can be selected to treat two or more patient diseases ordisorders, such as two or more patient diseases or disorders aredescribed herein.

Target tissue can comprise tissue of the terminal ileum, such as totreat hypercholesterolemia and/or diabetes. In these embodiments, thetarget tissue can extend into the proximal ileum and/or the colon.

Target tissue can comprise gastric mucosal tissue, such as tissueregions that produce ghrelin and/or other appetite regulating hormones,such as to treat obesity and/or an appetite disorder.

Target tissue can comprise bladder wall tissue, such as to treat adisease and/or disorder selected from the group consisting of:interstitial cystitis; bladder cancer; bladder polyps; pre-cancerouslesions of the bladder; and combinations of these.

Target tissue can comprise tissue selected from the group consisting of:large and/or flat colonic polyps; margin tissue remaining after apolypectomy; and combinations of these. These tissue locations can betreated to treat residual cancer cells.

Target tissue can comprise esophageal tissue and/or gastric tissue. Insome embodiments, target tissue comprises cancerous or precanceroustissue treated with a single or multiple energy deliveries, in single ormultiple clinical procedures. In some embodiments, target tissue istreated as a treatment of Barrett's esophagus.

Target tissue can comprise airway lining tissue, such as to treat adisease and/or disorder selected from the group consisting of:bronchoalveolar carcinoma; other lung cancers; pre-cancerous lunglesions; and combinations of these.

Target tissue can comprise at least a portion of the intestinal tractafflicted with inflammatory bowel disease, such that Crohn's diseaseand/or ulcerative colitis can be treated.

Target tissue can comprise tissue of the oral cavity, such as to treatone or more of: oral cancers and a pre-cancerous lesion of the oralcavity.

Target tissue can comprise tissue of the nasopharynx, such as to treatnasal polyps.

Target tissue can comprise GI tissue selected to treat Celiac diseaseand/or to improve intestinal barrier function.

The treatment assemblies, systems, devices and methods of the presentinventive concepts can be configured to avoid ablating or otherwiseadversely affecting certain tissue, termed “non-target tissue” herein.Depending on the location of tissue intended for treatment (i.e. targettissue), different non-target tissue can be applicable. In certainembodiments, non-target tissue can comprise tissue selected from thegroup consisting of: gastrointestinal adventitia; duodenal adventitia;the tunica serosa; the tunica muscularis; the outermost partial layer ofthe submucosa; ampulla of Vater such as during mucosal treatmentproximate the ampulla of Vater; pancreas; bile duct; pylorus; andcombinations of these.

The treatment assemblies, treatment elements and other functionalelements of the present inventive concepts can be configured toautomatically and/or manually expand in at least a radial direction.Typical expandable elements include but are not limited to: aninflatable balloon; a radially expandable cage or stent; one or moreradially deployable arms; an expandable helix; an unfurlable compactedcoiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of these. In some embodiments, theexpandable elements can comprise a radially expandable tube, such as asheet of material resiliently biased in a radially expanded conditionthat can be compacted through a furling operation, or a sheet ofmaterial resiliently biased in a radially compact condition that can beexpanded through an unfurling operation. The expandable elements cancomprise a foldable sheet, such as a sheet configured to be folded to beradially compacted and/or to be unfolded to radially expand. In someembodiments, the expandable elements expand to contact tissue, such asto expand to a diameter similar to the diameter of the luminal walltissue into which the expandable element has been placed. In someembodiments, the expandable elements expand to be closer to wall tissue,but remain at a distance (e.g. a fixed or pre-determined distance) fromthe tissue surface. In some embodiments, the expandable elements expandto be larger than the diameter of the luminal wall tissue into which theexpandable element has been placed, such as to improve the quality ofthe apposition of the expandable element against the uneven surface ofthe tissue. In these embodiments, the fully expanded diameter of theexpandable elements would be configured to avoid a diameter large enoughto cause lasting mechanical damage to the apposed tissue and/or totissue proximate the apposed tissue.

Any device of the present inventive concepts can include one or moretreatment elements configured to deliver energy to one or more energydelivery zones, to treat at least a portion of target tissue. Any devicecan include one or more fluid delivery elements, such as one or morenozzles configured to deliver fluid to tissue. The fluid deliveryelements can be constructed and arranged to deliver fluid to perform afunction selected from the group consisting of: expanding one or moretissue layers; warming or cooling tissue; removing debris or othersubstance from a tissue surface; delivering energy to an energy deliveryzone comprising a continuous or segmented surface; treating targettissue; and combinations of these. Any of the expandable assemblies ofthe present inventive concepts can include one or more other functionalelements, such as are described in reference to the figures herebelow.The treatment elements, fluid delivery elements, and/or other functionalelements can be mounted on, within (e.g. within the wall) and/or insideof an expandable element such as a balloon or expandable cage. In someembodiments, one or more functional elements is not mounted to anexpandable element, such as those attached to a shaft or othernon-expandable treatment device component.

In some embodiments, the treatment device comprises at least onetreatment element configured to deliver energy to an energy deliveryzone such as to ablate target tissue. Examples of ablation elementsinclude but are not limited to: an expandable reservoir such as aballoon configured to receive fluid at a temperature sufficient toablate tissue; fluid delivery elements configured to deliver ablativefluid directly to target tissue; a radiofrequency (RF) energy deliveryelement such as one or more electrodes; an ultrasonic transducer such asone or more piezo crystals configured to ablate tissue; a laser energydelivery element such as one or more optical fibers and/or laser diodes;a rotating ablation element; a circumferential array of ablationelements; and combinations of these.

The balloons of the present inventive concepts can be divided into twogeneral categories: those that are composed of a substantially elasticmaterial, such as silicone, latex, low-durometer polyurethane, and thelike; and those that are composed of a substantially inelastic material,such as polyethylene terephthalate (PET), nylon, high-durometerpolyurethane and the like. A third category includes balloons whichinclude both elastic and inelastic portions. Within the category ofelastic balloons, two subcategories exist: a first sub-category whereina combination of material properties and/or wall thickness can becombined to produce a balloon that exhibits a measurablepressure-threshold for inflation (i.e. the balloon becomes inflated onlyafter a minimum fluidic pressure is applied to the interior of theballoon); and a second sub-category, wherein the balloon expandselastically until an elastic limit is reached which effectivelyrestricts the balloon diameter to a maximum value. The individualproperties of the balloons in each of these categories can be applied toone or more advantages in the specific embodiments disclosed herein,these properties integrated singly or in combination. By way of exampleonly, one or more of the following configurations can be employed: ahighly elastic balloon can be used to achieve a wide range of operatingdiameters during treatment (e.g. during operation a desired balloondiameter can be achieved by adjustment of a combination of fluidtemperature and pressure); a substantially inelastic balloon or aballoon that reaches its elastic limit within a diameter approximating atarget tissue diameter (e.g. a duodenal mucosal diameter) can be used toachieve a relatively constant operating diameter that will besubstantially independent of operating pressure and temperature; aballoon with a pressure-threshold for inflation can be used to maintainan uninflated diameter during relatively low pressure conditions offluid flow and then achieve a larger operating diameter at higherpressure conditions of flow. Pressure-thresholded balloons can beconfigured in numerous ways. In one embodiment, a balloon is configuredto have a relatively thick wall in its uninflated state, such as tomaximize an electrically and/or thermally insulating effect while theballoon is maintained in this uninflated state. The balloon can befurther configured such that its wall thickness decreases during radialexpansion (e.g. to decrease an electrically and/or thermally insulatingeffect). In another embodiment, a balloon is configured to have arelatively small diameter in its uninflated state (e.g. a diameter thatis small relative to the inner diameter of tubular target tissue such asthe diameter of the mucosal layer of duodenal wall tissue), such as tominimize or completely eliminate apposition between the balloon and thesurrounding tissue to minimize heat, RF and/or other energy transferinto the surrounding tissue until the balloon is fully inflated. Inanother embodiment, a balloon and an ablation system or device areconfigured to circulate a flow of fluid through the balloon (e.g. anelastic balloon or an inelastic balloon) at a sufficiently low enoughpressure to prevent apposition of the balloon or other device componentwith target tissue, such as to pre-heat one or more surfaces of theablation system or ablation device that are in fluid communication withthe balloon. In this configuration, when the balloon or other ablationelement is positioned to deliver energy to target tissue, thetemperature of the balloon or other ablation element will be at adesired level or it will rapidly and efficiently reach the desired levelfor treatment (i.e. minimal heat loss to the fluid path components dueto the pre-heating or pre-cooling). These configurations provide amethod of delivering energy to tissue with an ablative fluid filledballoon. A “thermal priming” procedure can be performed prior to one ormore target tissue treatments, such as to improve thermal response timeof one or more portions of the treatment device. Ablative fluid filledballoon treatment devices as well as thermal priming devices and methodscan be configured as is described in applicant's co-pendingInternational PCT Application Serial Number PCT/US2013/28082, entitled“Heat Ablation Systems, Devices and Methods for the Treatment ofTissue”, filed Feb. 27, 2013, the contents of which is incorporatedherein by reference in its entirety.

At times during target tissue treatment when it is desirable toinitiate, increase and/or otherwise modify the treatment of tissue byone or more tissue treatment elements (e.g. a fluid delivery elementdelivering ablative fluid, a mechanically abrasive element, a hot orcold fluid balloon delivering a thermal energy to tissue and/or anelectrode delivering RF energy), the treatment assembly diameter (e.g.the diameter of a balloon, deployable cage, expandable tube or otherexpandable assembly) can be increased in situ to move a treatmentelement closer to target tissue and/or to change the contact forcebetween the treatment element and the target tissue. At times duringtreatment when it is desirable to stop or otherwise decrease the amountof tissue treatment, the treatment assembly diameter can be reduced insitu, such as to prevent or reduce delivery of energy or other treatmentto the target tissue by eliminating or reducing tissue contact of one ormore treatment elements (e.g. electrodes, abrasive surfaces or ablativefluid filled balloons). For those cases where the native diameter of thetarget tissue varies substantially within the treatment zone, then ahighly elastic or compliant balloon or other expandable element can beemployed, such as a balloon or deployable cage which can be adjusted toachieve a wide range of operating diameters.

Alternatively or additionally, to initiate, increase and/or otherwisemodify the treatment of tissue by one or more treatment elements (e.g. afluid delivery element delivering ablative fluid, a mechanicallyabrasive element, a hot or cold fluid balloon delivering thermal energyto tissue and/or an electrode delivering RF energy), the diameter of thetarget tissue can be decreased in situ to move target tissue closer to atreatment element and/or to change the contact force between the targettissue and the treatment element. To stop or otherwise decrease ablationof tissue, the diameter of tissue neighboring a treatment element can beincreased in situ, such as to prevent or reduce delivery of energy orother treatment to the target tissue by eliminating or reducing tissuecontact of one or more treatment elements (e.g. electrodes, abrasivesurfaces or ablative fluid filled balloons). The diameter of the tissueproximate a treatment element can be increased or decreased, independentof the treatment assembly diameter, by means of delivering and/orwithdrawing a fluid, to and/or from a lumen surrounded by target tissue,such as by using standard GI insufflation techniques. Typicalinsufflation fluids include but are not limited to: gases such as carbondioxide or air; liquids such as water or saline solution; andcombinations of these. The insufflation fluids can be introduced througha treatment device, through an endoscope such as an endoscope throughwhich the treatment device is inserted, and/or via another device placedproximate the target tissue. Delivery of insufflation fluids can beperformed to move target tissue away from one or more treatmentelements, such as to stop transfer of energy to target tissue at the endof a treatment of target tissue as described hereabove. Alternatively oradditionally, delivery of insufflation fluids can be performed tomanipulate tissue, such as to distend and/or elongate tissue. Removal ofthese insufflation fluids and/or the application of a vacuum or othernegative pressure can be used to decrease the diameter of the targettissue, such as to bring the target tissue in closer proximity to one ormore treatment elements and/or to increase the contact force betweentarget tissue and one or more treatment elements, also as describedhereabove. In this tissue diameter controlled approach, a treatmentassembly including a balloon that can be maintained at a substantiallyconstant diameter can be desirable, such as a substantially inelasticballoon such as a balloon with an elastic-limit.

Referring now to FIG. 1, a flow chart of a method of treating targettissue in a patient is illustrated, consistent with the presentinventive concepts. The method includes providing at least a tissuetreatment element configured to deliver energy to tissue. A tissuetreatment system can be provided, such as system 10 of FIG. 3, includingtreatment element assembly 140 as described herebelow. Target tissue istreated, such as target tissue of the GI tract, by causing the treatmentelement to deliver energy to tissue in an energy delivery zone, asdefined hereabove. The energy delivery causes a reduction in the surfacearea of tissue, such as a reduction in the luminal surface area of oneor more portions of the GI tract.

In STEP 10, a patient assessment is performed such as to diagnose,prognose or otherwise assess one or more diseases or disorders of apatient. STEP 10 can include selecting a mammalian patient (e.g. ahuman) for receiving a method of the present inventive concepts. Ifselected, STEPs 20 through 70 can then be performed.

In STEP 20, target tissue to be treated is selected. Target tissue caninclude multiple tissue segments to be treated simultaneously orsequentially as described herein. In subsequent steps, additional targettissue can be identified for treatment, and previously identified targettissue can be removed from consideration of treatment. Target tissue caninclude but is not limited to: mucosa; mucosa through superficialsubmucosa; mucosa through mid-submucosa; mucosa through deep-submucosa;and combinations of these. Target tissue segments can comprise length(e.g. axial length), width (e.g. an arc length dimension such as thepartial or full circumference of a surface or layer of tubular tissue)and depth dimension. In some embodiments, an axial length dimension ofeach target tissue segment is less than 20 cm in length, less than 15 cmin length, less than 10 cm, less than 5 cm in length or less than orequal to 3 cm in length. In some embodiments, a cumulative sum of allthe target tissue axial segment length dimensions is less than 100 cm,or less than 50 cm (i.e. less than 100 cm or less than 50 cm,respectively, of the GI tract is treated).

In STEP 30, one or more treatment devices are selected, such as thosedescribed in reference to FIG. 3 and FIG. 5 herebelow. The treatmentdevices provide a tissue treatment element constructed and arranged todeliver energy.

STEPs 40 comprise STEP 41, STEP 42 and STEP 43. Any of STEPs 41, 42 and43 can be performed multiple times, in various orders, such as when thetarget tissue comprises multiple tissue segments that are treatedsequentially. STEPs 40 can be performed with one or more components ofsystem 10 of FIG. 3 described herebelow. One or more devices can beinserted into the body over a guidewire and/or through an endoscope,such as a sizing element, a tissue expansion element and/or a tissuetreatment element that is inserted into the patient's body over aguidewire or through an endoscope.

In STEP 41, a portion of the patient's anatomy is measured, such as tomeasure one or more diameters (e.g. one or more diameters of in innersurface of an axial segment of the duodenum or jejunum), radius ofcurvature, or other geometric analysis of tissue such as a volume oftissue such as a target tissue volume, or a surface area of tissue suchas a surface area of an energy delivery zone. In some embodiments, theanatomical measurement is performed using one or more devices orcomponents of system 10 of FIG. 3 described herebelow, such as sizingdevice 430.

In STEP 42, one or more tissue layers of the patient are expanded, suchas with a tissue expansion device and/or tissue expanding element suchas those described in applicant's co-pending International PCTApplication Serial Number PCT/US2013/37485, entitled “Tissue ExpansionDevices, Systems and Methods”, filed Apr. 19, 2013, the contents ofwhich is incorporated herein by reference in its entirety. The tissuelayers expanded can comprise target tissue and/or non-target tissue. Insome embodiments, one or more measurement procedures of STEP 41 isperformed to measure the expansion, changes or other dimensionalinformation caused or otherwise related to one or more tissue expansionsperformed in one or more STEPs 42. In some embodiments, the expandedtissue comprises one or more layers of submucosal tissue. In someembodiments, tissue is expanded to flatten plicae of the GI tract.Tissue expansion can be accomplished with one or more fluid deliveryelements, such as a fluid delivery element selected from the groupconsisting of: needle; water jet; iontophoretic fluid delivery element;and combinations if these, such as those described in reference to FIG.3 herebelow. One or more fluid delivery elements can be part of a fluiddelivery assembly, such as a fluid delivery assembly of system 10 ofFIG. 3. A fluid delivery assembly can include reservoirs or boluses ofpredetermined amounts of fluid, such as a volume of fluid for aninjection that is at least 1 ml, or between 2 ml and 5 ml. Fluid can beinjected to multiple injection sites, such as a set of multipleinjection sites selected from the group consisting of: at least threeinjection sites along a circumference of tubular tissue, where a firstinjection site can be separated from a second injection site byapproximately 1 cm, or between 0.5 cm to 5 cm, or between 1 cm and 3 cm,or between 1 cm and 2 cm; two or more injection sites that are axiallyand/or radially spaced; two or more injections sites that are separatedbased on the diameter of the tubular tissue into which they areinjected; and combinations of these. Fluid can be injected with theassistance of one or more vacuum applying elements, such as thosedescribed in reference to FIG. 3 herebelow. Injected fluid can comprisea material selected from the group consisting of: water; saline; gel;and combinations of these. In some embodiments, injected fluid comprisesa protein hydrogel.

Tissue expanded in STEP 42 can comprise one or more layers ofgastrointestinal tissue, such as one or more layers of duodenal and/orjejunal tissue. The one or more tissue layers can comprise one or morelayers of submucosal tissue.

In STEP 43, target tissue is treated, such as with the one or moretreatment devices selected in STEP 30. STEP 43 includes the treatment oftarget tissue with one or more treatment elements to deliver energy toone or more energy delivery zones within the patient's GI tract or otheranatomical location as described herein. The energy delivered causes areduction in luminal surface area of one or more portions of thepatient's GI tract. The reduction in surface area can be a reduction inthe surface area of the target tissue treated and/or a reduction in GIluminal surface area that results after new tissue forms as a result ofthe target tissue treatment (e.g. new tissue that replaces the treatedtarget tissue).

In some embodiments, energy delivery during STEP 43 can be modified(e.g. initiated, stopped, increased and/or decreased) by changing (i.e.increasing or decreasing) the cross-sectional area of tissue surroundinga tissue treatment element. This decrease can be caused by means ofdelivering and/or withdrawing a fluid, to and/or from a lumen surroundedby target tissue, such as by using standard GI insufflation techniqueswith an insufflation device of the system of the present inventiveconcepts, as described hereabove. In some embodiments, apposition of atissue treatment element is measured, such as to determine if sufficientcontact is present between a tissue treatment element and target tissue.

Target tissue treatment of STEP 43 can be performed at a time related tothe time of one or more tissue expansions performed in a previouslyperformed STEP 42. In some embodiments, target tissue that has beenexpanded is treated at least 1 minute after expansion, or at least 5minutes after expansion. In some embodiments, target tissue is treatedwithin at least 20 minutes of expansion. In some embodiments, expandedtissue comprises an inner layer of an axial segment of duodenal and/orjejunal tissue, and energy is delivered to an energy delivery zoneincluding multiple, discontinuous partial circumferential portions ofthe axial segment. In these embodiments, energy is not delivered to atleast one partial circumferential tissue portion between two of thetreated portions of the axial segment, such as is described in detail inreference to FIG. 7A-7C herebelow.

In some embodiments, STEPs 41, 42 and 43 are performed multiple times,such as to measure, expand and treat multiple tissue segments along thelength of the GI tract, such as along a length of the duodenum and/orjejunum of the patient. In some embodiments, a series of geometrymeasurements of STEP 41 are performed continuously, after which a seriesof tissue expansions of STEP 42 are performed continuously, after whicha series of tissue treatments of STEP 43 are performed continuously.Alternatively or additionally, one or more of STEPs 41, 42 and 43 areperformed in between one or more of the other steps in an alternatingfashion.

In some embodiments, between two and fifty energy delivery zones receiveenergy from a treatment element, such as in one to fifty STEP 43's. Themultiple energy delivery zones can receive energy simultaneously orsequentially, such as within a twenty-four hour period. In someembodiments, a second procedure as described herein is performed, wherea second energy delivery zone receives energy between twenty-four hoursand six months after a first energy delivery zone receives energy.Multiple energy delivery zones can have overlapping and/or similarboundaries (e.g. proximal or distal boundaries), as described in detailin reference to FIG. 4 herebelow. Any of the multiple energy deliveryzones can include a full or partial circumferential segment of tubulartissue, such as a full or partial circumferential portion of an axialsegment of duodenal and/or jejunal tissue.

In STEP 50, the condition of the patient is assessed. STEP 50 can beperformed at any time during the clinical procedure, or at a timesubsequent to the clinical procedure, such as 1 week, 1 month, 3 months,6 months or longer from the time of the clinical procedure.

In STEP 60, a determination is made whether a second treatment should beperformed on the patient, such as a treatment including STEP 20 throughSTEPs 40 described hereabove. If a repeat procedure is deemed necessary,STEP 10 and one or more subsequent steps can be repeated. If a repeatprocedure is deemed unnecessary at that time, STEP 70 is performed.

In STEP 70, a post-tissue treatment procedure can optionally beperformed on the patient. In STEP 70, the patient can receive additionalmedical treatments including one or more pharmaceutical treatments suchas a treatment including a pharmaceutical drug or other agent selectedfrom the group consisting of: an anti-inflammatory agent such as asteroid; an immunomodulator such as Sirolumus or Tacrolimus; Sucralfate;a bismuth compound; an acid inhibitor; a proton-pump inhibitor; aH2-receptor blocker; an antibiotic; an anti-fungal; an appetitesuppressant agent; an anti-obesity agent; an anti-cholesterol agent; adiabetes drug such as metformin, a GLP-1 analogue, a DPP-IV inhibitor,sulfonulereas, insulin, or an insulin analog; and combinations of these.Alternatively or additionally, the treatment can include the patientundertaking a specific diet, such as a low calorie diet. In someembodiments, the low calorie diet comprises a diet including less than1500 calories per day, or less than 1000 calories per day. The diet caninclude minimizing the content of one or more substances, such asfructose, simple sugars or fats. In some embodiments, a low calorie dietis maintained during a period of time in which at least some mucosalregrowth occurs. The period after the delivery of energy can becharacterized by an intense phase of mucosal regrowth, during which timethe epithelial surface reconstitutes itself to provide a mucosal barrieragainst the environment. At the same time, the cellular architecture ofthe mucosa is restored in such a way as to facilitate the properphysiologic functioning of the region that was treated with energy. Thephysiologic function of the mucosal layer can be influenced by dietarymodifications or pharmaceutical agents that affect cellularproliferation or growth by altering the number or types of cells thatcomprise the reconstituted mucosa. A low calorie diet, for instance, canstimulate the growth of less total mucosal mass than a high caloriediet, and can also influence the number and type of hormone-producingcells that differentiate from the stem cells that give rise to thereconstituted mucosa.

After STEP 70, STEP 50 can be re-performed, such as after an elapsedtime of at least 6 months or at least one year later.

In the method of FIG. 1, the patient can be selected for treatment ofone or more diseases or disorders such as those described hereabove. Insome embodiments, the patient is selected to treat a disease or disorderselected from the group consisting of: diabetes; pre-diabetes; impairedglucose tolerance; insulin resistance, and combinations of these. Insome embodiments, the patient is selected to treat a disease or disorderselected from the group consisting of: obesity or otherwise beingoverweight; hypercholesterolemia; exercise intolerance; psoriasis;hypertension; hypertriglyceridemia; metabolic syndrome; and combinationsof these. The method can be performed after the patient has exhibitedone or more symptoms of a disease state for a period of time, such as atleast 1 year, at least 2 years or at least 5 years. In some embodiments,the patient is selected to treat type 2 diabetes. In some embodiments, adiabetic patient is treated within a time period of exhibiting diabeticphysiology, such as a time period of less than 10 years, less than 5years, less than 2 years or less than 1 year. In some embodiments, apatient selected for treatment has an HbA1c level of at least 7.5% or atleast 8%.

The method of FIG. 1 can be performed to cause a reduced absorptive(e.g. reduced absorption of nutrients) and/or reduce secretory capacity(e.g. reduced secretion of gut hormones) due to the reduction of luminalsurface area of at least a portion of the GI tract. In some embodiments,reduced absorption of at least one of glucose, cholesterol, amonoglyceride or a free fatty acid is achieved. The method can beconstructed and arranged to cause a reduction in glucose absorptionand/or gut hormone release in a surface area reduced portion of the GItract, such as a reduction that is present in these areas during and/orafter food intake by the patient. In some embodiments, a reduced releaseof GIP and/or another proximal gut hormone results in the surface areareduced portion of the GI tract.

The amount of target tissue selected and/or treated (e.g. including oneor more continuous or discontinuous tissue segments) can beproportionally related to the longevity of the disease state beingtreated. The amount of target tissue selected and/or treated cancomprise a volume of tissue, such as the cumulative volume of multiplecontinuous and/or discontinuous tissue segments. Alternatively oradditionally, the amount of target tissue selected and/or treated can berepresented by a length of tubular tissue, such as the cumulative lengthof multiple continuous and/or discontinuous axial tubular (e.g.duodenal) tissue segments each of which receives energy on one or moreportions of at least 50% of its inner surface (i.e. the energy deliveryzone comprises at least 50% of the inner surface of the cumulativelengths of axial tubular tissue segments). Alternatively oradditionally, the amount of target tissue selected and/or treated can berepresented by an amount of tissue surface area of tissue receivingenergy, such as the cumulative surface area of multiple continuousand/or discontinuous tissue portions each of which receives energy onone or more portions of at least 50% of its inner surface (i.e. theenergy delivery zone comprises at least 50% of the inner surface of themultiple tissue portions).

In some embodiments, the disease state comprises a diabetes state andthe following proportions of target tissue treated apply: the energydelivery zone comprises less than 50% of the duodenal mucosal surfacearea if the patient has exhibited diabetic physiology for less than 3years; the energy delivery zone comprises less than 50% of the duodenalmucosal surface area if the patient has exhibited diabetic physiologyfor less than 5 years; the energy delivery zone comprises less than 75%of the duodenal mucosal surface area if the patient has exhibiteddiabetic physiology for less than 7 years; or the energy delivery zonecomprises less than 75% of the duodenal mucosal surface area if thepatient has exhibited diabetic physiology for less than 10 years. Inthese and other embodiments, the percentage of the energy delivery zonereceiving energy can be between 0.01% and 100% of the surface area ofthe energy delivery zone, such as at least 2%, at least 5%, at least 10%or at least 20% of the surface area of the energy delivery zone.

In some embodiments, the disease state comprises a diabetes state andthe following proportions of target tissue treated apply: the energydelivery zone comprises less than 50% of the duodenal mucosal surfacearea if the patient has an HgbA1c level less than 8; the energy deliveryzone comprises less than 50% of the duodenal mucosal surface area if thepatient has an HgbA1c level less than 9; the energy delivery zonecomprises less than 75% of the duodenal mucosal surface area if thepatient has an HgbA1c level less than 10; or the energy delivery zonecomprises less than 75% of the duodenal mucosal surface area if thepatient has an HgbA1c level less than 12. In these and otherembodiments, the percentage of the energy delivery zone receiving energycan be between 0.01% and 100% of the surface area of the energy deliveryzone, such as at least 2%, at least 5%, at least 10% or at least 20% ofthe surface area of the energy delivery zone.

In some embodiments, the target tissue and/or the energy delivery zoneis selected based on patient characteristics. Applicable patientcharacteristics include but are not limited to: duration of diabetes;HbA1c; area under the curve of a glucose tolerance test; area under thecurve of a mixed meal tolerance test; C-peptide level; GIP level; GLP-1level; age; BMI; and combinations of these. In some embodiments, thetarget tissue and/or the energy delivery zone is selected based on atarget diabetes endpoint results, such as the result determined in oneor more diagnostic tests. Applicable diabetic endpoint results includebut are not limited to: target HbA1c level; target BMI; target areaunder the curve of glucose tolerance test; target cholesterol level;target triglyceride level; and combinations of these.

In some embodiments, the energy delivery zone comprises an anatomicallocation selected from the group consisting of: inner surface portion ofstomach; full circumferential inner surface of an axial segment ofduodenum; partial circumferential inner surface of an axial segment ofduodenum; full circumferential inner surface of an axial segment ofjejunum; partial circumferential inner surface of an axial segment ofjejunum; and combinations of these. The energy delivery zone and/ortarget tissue can include at least one axial segment of the duodenumand/or jejunum, such as tissue comprising at least mucosal tissue of theduodenum and/or jejunum. The at least one axial segment of target tissueand/or energy delivery zone treated can include a full or partialcircumferential segment of GI tissue. In some embodiments, a partialcircumferential segment to be treated comprising 45° to 350° of an axialsegment of tubular tissue. In additional to duodenal and/or jejunalmucosal tissue, target tissue can include tissue selected from the groupconsisting of: ileal mucosal tissue; gastric mucosal tissue; andcombinations thereof.

Target tissue treated and/or an energy delivery zone can be positionedrelative to one or more anatomical structures, such as to ensure and/orimprove therapeutic benefit, and/or to prevent damage to tissue orprevent any undesired clinical event. In some embodiments, target tissueand/or an energy delivery zone comprises at least one tissue segmentcomprising tubular tissue with a proximal end and a distal end, such asa relatively continuous axial segment of one or more full or partialcircumferential tissue layers or surfaces of the duodenum. In someembodiments, the target tissue and/or energy delivery zone proximal endis positioned distal to (i.e. away) from the ampulla of Vater, butwithin 5 cm or within 2 cm of the ampulla of Vater, such as when theampulla of Vater is located and/or otherwise identified prior to one ormore energy deliveries to treat target tissue. In some embodiments,tissue treatment element treats target tissue proximal to but in closeproximity to the ampulla of Vater (e.g. delivers energy to an energydelivery zone proximal to but in close proximity to the ampulla ofVater). The target tissue and/or energy delivery zone proximal end canbe positioned at least 10 cm from the pylorus, or at least 15 cm fromthe pylorus. The target tissue and/or energy delivery zone proximal endcan be positioned distal to the duodenal bulb. In some embodiments, thetarget tissue and/or energy delivery zone proximal end is positioned ata location in the duodenum that includes the most proximal location inthe duodenum that includes plicae circulares. In some embodiments, thetarget tissue and/or energy delivery zone proximal end is positioned ata location within 5 cm of the ampulla of Vater and the distal end islocated proximal to the ligament of Treitz.

As stated above, the energy delivery zone can comprise multiple energydelivery zones that receive sequential deliveries of energy, such assequential deliveries of energy received from a single energy deliveryelement or other tissue treatment element (e.g. a hot fluid balloon orelectrode array) that translates within the GI tract from a first energydelivery zone to a second energy delivery zone between energydeliveries. In some embodiments, each energy delivery zone comprises alength from a proximal end to a distal end of at least 3 cm or at least5 cm. In some embodiments, an energy delivery zone can comprise a lengthfrom its proximal end of at least 10 cm or at least 50 cm, such as whena single or few energy delivery zones receive energy during a singleclinical procedure.

In some embodiments, at least one portion (e.g. at least one axialsegment) of an inner surface of the duodenum and/or jejunum does notreceive energy from a treatment element. The at least onenon-energy-receiving surface can comprise a segment of mucosa thatincludes minimal or no plicae circulares. Alternatively or additionally,the at least one non-energy-receiving surface can comprise a segment ofthe duodenum and/or jejunum with a sharp bend, such as a curved segmentof tubular tissue with an average radius of curvature less than 5 cmover a 75° arc, or less than 3 cm over a 75° arc, as described herebelowin reference to FIG. 6. Similarly, in some embodiments, one or moreenergy delivery zones can comprise the inner surface of relativelylinear tubular tissue segments, while segments with a higher radius ofcurvature are avoided. In these embodiments, the energy delivery zonecan comprise the inner surface of one or more full circumferentialsegments of tubular tissue. In some embodiments, at least a portion ofan inner surface of tubular tissue may not receive energy from a tissuetreatment element due to the inner surface topography that can resultduring a tissue expansion procedure (e.g. a submucosal tissue expansionprocedure as described herein), such as when one or more valleys createdby the tissue expansion do not receive energy delivered by a tissuetreatment element, as described in detail below in reference to FIGS.7A-7C.

In some embodiments, a relatively small proportion of an energy deliveryzone receives energy from a tissue treatment element, such as isspecifically described in reference to treatment device 500 of FIGS. 5Aand 5B described herebelow. In this “fractional” approach, smallportions of the entire surface of one or more energy delivery zonesreceive energy, such as light energy or electromagnetic energy (e.g. RFenergy). In some embodiments, the portions of the tissue surfacesreceiving energy can be sufficiently small such that the total amount ofheat generated is minimal. One advantage of this fractional method is toreduce adverse effects of one or more overlapping treatments (e.g.reduce likelihood of damage to non-target tissue), such as to alleviatethe requirement of precise positioning of a delivery element orotherwise reduce the precision required in energy delivery. In someembodiments, the energy delivery zone is between 1 cm² and 5 cm². Thesmall portions of a tissue surface receiving energy result in multipletreated target tissue segments that each includes an inward facingsurface relatively positioned on the tissue surface receiving theenergy. Non-target or other tissue not receiving energy can bepositioned between the multiple treated target tissue segments. Thesetreated target tissue segments extend into the tissue, such as deeperinto the wall of tubular tissue such as deeper through a mucosal layerand at least partially into a submucosal layer. In some embodiments, thetarget tissue segments inward facing surfaces collectively comprise aquantity of 50 to 3000 per square centimeter of tissue surface receiveenergy, such as approximately a quantity of 500 per square centimeter.The target tissue inward facing surfaces can each comprise a surfacewith an equivalent diameter of between 20 and 200 microns (i.e. asurface whose area is equivalent to a circle with a diameter between 20and 200 microns). The target tissue inward facing portions positionedwithin an energy delivery zone can be treated sequentially, such as asequential energy delivery by a scanning light delivery element and/orsequentially activated electrodes delivery RF energy. Alternatively oradditionally, multiple target tissue inward facing portions positionedwithin an energy delivery zone can be treated simultaneously, such asvia a light source that delivers multiple rays of light to a tissuesurface simultaneously (e.g. as described in reference to FIG. 5herebelow), or an array of micro-electrodes that delivers monopolarenergy to small portions of tissue simultaneously. A set of energydelivery zones can each comprise an axial length of between 0.5 and 3 cmin length. A tissue treatment element can be translated between energydeliveries, such as a translation of approximately between 0.5 cm and 3cm, such as to allow a slight overlap between any two energy deliveryzones, such as to cause a mating of boundaries of any two energydelivery zones and/or such as to provide a gap between any two energydelivery zones.

In this fractional approach, the ratio of energy delivery zone tissuereceiving energy to energy delivery zone tissue not receiving energy canbetween 0.1% and 90%, such as less than 50%, less than 20%, less than10%, less than 5%, less than 2% or less than 1%. The target tissuesegment inward facing surfaces can comprise a major axis of less than orequal to 100 microns. The target tissue can be exposed to a temperaturegreater than or equal to 60° C., between 60° C. and 80° C., or atemperature greater than or equal to 100° C. In some embodiments, atleast a portion of the target tissue is vaporized. Energy delivered tothe energy delivery zones in this fractional approach can compriseenergy selected from the group consisting of: RF; ultrasound; laserlight; non-laser light such as non-laser light from an LED; chemical;and combinations of these. In some embodiments, the fractional approachenergy delivered is laser or other light energy, such as light energydelivered element by a rotating element as is described in reference toFIG. 5 herebelow. In some embodiments, the fractional approach energydelivery comprises RF energy delivery, such as monopolar or bipolar RFenergy delivery from an array of electrodes as described in reference toFIG. 3 herebelow. In some embodiments, the fractional approach involvesexpanding one or more layers of tissue, as described herein. In theseembodiments, the tissue can be expanding with a fluid comprising aninjectable non-energy absorbing material. Alternatively or additionally,fluid can be expanded with an injectable energy absorbing material, suchas water or saline.

The method of FIG. 1 can be accomplished with a tissue treatment systemor device, such as system 10 or one or more components or assemblies ofsystem 10 described herebelow in reference to FIG. 3. The tissuegeometry measurement procedures of STEP 41, the tissue expansionprocedures of STEP 42, the tissue treatment procedures of STEP 43 and/oranother portion of the method of FIG. 1 can be performed with one ormore components or assemblies of system 10 of FIG. 3. In someembodiments, the method of FIG. 1 is performed while controlling one ormore system parameters, such as a system parameter selected from thegroup consisting of: a priming procedure parameter such as primingtemperature or priming duration; target tissue treatment parameter suchas target tissue temperature or target tissue treatment duration; fluidflow rate such as treatment fluid flow rate; a pressure parameter suchas a treatment element pressure maintained during treatment of targettissue; a treatment element diameter such as a treatment elementdiameter maintained during treatment of target tissue; and combinationsof these. One or more tissue treatment elements can be varied orotherwise controlled during the method of the present inventiveconcepts. In some embodiments, a controlled tissue treatment elementparameter comprises a parameter selected from the group consisting of:thermal dose delivered; priming temperature; tissue treatmenttemperature; fluid flow rate; pumping pressure; vacuum pressure; tissuetreatment time; and combinations of these. In some embodiments, thediameter of an expandable tissue treatment element such as a balloon iscontrolled. In these embodiments, a balloon characteristic such asballoon diameter versus pressure is selected in STEP 30.

In some embodiments, the tissue treatment element of the method of FIG.1 provides an ablative treatment to the energy delivery zone and/or thetarget tissue, such as an ablative treatment selected from the groupconsisting of: delivery of thermal energy from a balloon filled withfluid at an ablative temperature; RF energy ablation; delivery of anablative fluid directly to tissue; cryoablation; delivery of laserenergy; delivery of sound energy such as subsonic sound energy orultrasonic sound energy; plasma energy delivery; argon plasmacoagulation; microwave energy delivery; delivery of non-laser lightenergy; and combinations of these. Alternatively or additionally, thetissue treatment element can be constructed and arranged to provide anon-ablative energy treatment to the energy delivery zone and/or thetarget tissue, such as a non-ablative energy treatment selected from thegroup consisting of: mechanical removal of mucosal tissue; chemical,sclerosant or pharmaceutical injection into the submucosa; radioactiveseed deposition; chemical spray such as an acid spray; pharmacologicadministration such as drug delivery via an agent-eluting balloon; andcombinations of these. In some embodiments, a non-ablative tissuetreatment element comprises a cutter or other element constructed andarranged to resect tissue, such as to resect plicae tissue, mucosaltissue and/or submucosal tissue of the duodenum and/or the jejunum. Forexample, a non-ablative treatment element can be configured to resectpeaks of the plicae including much of the mucosa, such as to leave athin layer of submucosa on which new mucosa could grow.

As described above, a tissue treatment element and or tissue treatmentsystem, such as those described in reference to FIG. 3 herebelow, cantreat target tissue in multiple tissue treatment steps. The multipletissue treatment steps can comprise one or more of: multiple sequentialdeliveries of energy to tissue; multiple sequential deliveries ofablative fluid to tissue; multiple sequential mechanical abrasions ormechanical cutting of tissue; and one or more expansions of one or morelayers of tissue.

In some embodiments, target tissue is treated with a series of energydeliveries to each energy delivery zone, after which a relativelyuniform advancement of the tissue treatment element is made, such as tosequentially treat relatively continuous (e.g. side-by-side) energydelivery zones. Alternatively, non-bordering energy delivery zones canbe treated with sequential deliveries, such as to avoid heating oftissue in a particular anatomical location, each as described inreference to FIGS. 4 and 6 herebelow.

The method of the FIG. 1 is constructed and arranged to cause a luminalsurface area reduction in at least a portion of GI tract. In someembodiments, the surface area reduction occurs at least one day afterdelivery of energy to the energy delivery zone, or at least one week orone month after the delivery of energy to the energy delivery zone. Insome embodiments, the surface area reduction occurs in less than a dayafter treatment, such as a fractional treatment using laser or RF energydelivered to an energy delivery zone. For example, ablative removal oftissue in one or more divots, valleys and/or folds causes the tissuesurrounding the removed tissue to simply close up, bringing the edgestogether and thus reducing the surface area. The surface area reductionof the present inventive concepts can comprise a reduction in a GItissue characteristic selected from the group consisting of: averageheight of mucosal folds; surface area of mucosal folds; number ofmucosal folds; and combinations of these. In some embodiments, thetarget tissue treatment reshapes mucosal tissue, such as a flattening ofmucosal tissue or other mucosal tissue change that can occur at least 7days after treatment of the target tissue. In some embodiments, thetarget tissue treatment results in a reduction in the average villilength in a portion of the GI tract and/or a reduction in the number ofvilli in a portion of the GI tract.

In some embodiments, the target tissue treatment reshapes and/or reducesthe volume of submucosal tissue. In these embodiments, one or more ofthe following submucosal tissue changes can after the treatment;flattening of the submucosal tissue; increased uniformity of thickness;increased averaged minimum thickness; reduced volume of submucosaltissue; and combinations thereof. In some embodiments, submucosal tissuecan be vaporized and/or the delivery of energy to an energy deliveryzone can cause coagulation necrosis where the tissue is resorbed throughnormal healing process. Target tissue treatment can cause a healingresponse in tissue that results in a reduced amount of mucosal tissue(e.g. in that portion of the GI tract). The submucosal tissuemodification can be a result of a target tissue treatment includingcontrolled thermal heating, such as controlled thermal heating by atissue treatment element constructed and arranged to shrink and/ordenature collagen in a submucosal or other tissue layer. In someembodiments, one or more submucosal tissue modifications can occur atleast 7 days after the target tissue treatment is performed.

In some embodiments, the target tissue treatment results in one or moreof: a smoother surface in a portion of the GI tract; a reduced number ofplicae circulares in a portion of the GI tract; or a reduction in theluminal surface area in a portion of the GI tract. In some embodiments,the target tissue treatment results in a modification or other treatmentof stem cells, such as to remove and/or ablate one or more of mucosalstem cells and/or epithelial stem cells. In some embodiments, the targettissue treatment results in a reduction in the number of the number ofenteroendocrine cells and/or absorptive cells in a portion of the GItract.

The luminal surface area reduction of one or more portions of the GItract can occur at a time at least 7 days after treatment of the targettissue, such as when the surface area reduction initiates at a timeduring target tissue treatment or any time thereafter. In someembodiments, the surface area reduction is occurring at least 3 weeks orat least 6 weeks after target tissue treatment. The method of thepresent inventive concepts can be constructed and arranged such that thereduced luminal surface area of one or more portions of the GI tractlasts for at least 3 weeks, or at least 6 weeks. Alternatively oradditionally, the method of the present inventive concepts can beconstructed and arranged to provide a therapeutic benefit to the patientthat lasts for at least 6 weeks, or at least 6 months, or at least 2years. In some embodiments, a second target tissue treatment (e.g. asecond clinical procedure as described herein performed at least 6 weeksafter the first clinical procedure) is performed to extend the longevityof the surface area reduction and/or the therapeutic benefit achievedvia the surface area reduction.

The luminal surface area reduction of one or more portions of the GItract can include a reduction in luminal surface area of one or moreportions of the duodenum and/or jejunum. The reduced surface area of theduodenum and/or jejunum can comprise at least 5%, at least 10%, at least20%, at least 50% or at least 90%, of the surface area of the duodenumand/or jejunum, respectively.

In some embodiments, STEP 30 includes selecting from a kit of treatmentelements, such as selecting from a kit of treatment devices described inreference to FIG. 3 herebelow. The selection can include selecting asize of a treatment element, such as the diameter of a treatmentelement. Alternatively or additionally, a treatment element size can bevaried or otherwise controlled, such as in one or more of STEPs 40. Insome embodiments, a treatment element is selected and/or controlled tobe within a diameter between 10 mm and 40 mm, such as between a diameterbetween 15 mm and 32 mm. In some embodiments, a treatment element isdeflected during the clinical procedure, such as deflection of acatheter shaft including the treatment element, such as via one or morepull wires. In some embodiments, a treatment element is rotated, such asa rotation that is performed prior to, during and/or subsequent toenergy delivery to the energy delivery zone by the treatment element.The selected treatment element can comprise one or more expandableelements, such as an element constructed and arranged to expand to adiameter between 10 mm and 40 mm, or between 15 mm and 32 mm, or between19.0 mm and 27.5 mm. Expandable treatment elements can include but arenot limited to an element selected from the group consisting of:balloon; expandable cage; radially deployable arm; and combinations ofthese.

The one or more treatment elements used to treat target tissue in STEP43 can have one or more of numerous forms such as those described inreference to FIG. 3 herebelow. A treatment element can comprise anenergy delivery element such as a hot fluid balloon, an RF energydelivery element, an ultrasound energy delivery element, a laser orother light energy delivery element, or combinations of these. Atreatment element can be configured to ablate tissue such a hot fluidballoon constructed and arranged to receive fluid at a temperaturegreater than or equal to 90° C., and then treat target tissue as thetemperature decreases to a temperature greater than 70° C. during thecourse of treatment. In some embodiments, a bolus of heated fluid isprovided to a treatment element balloon. Alternatively, a recirculatingfluid can be provided to a treatment element balloon. An RF energydelivery element can include an expandable element such as an expandablecage or expandable balloon comprising one or more electrodes constructedand arranged to deliver monopolar and/or bipolar energy to tissue. Atreatment element can comprise a tissue cutting element, such as acutter configured to cut tissue during advancement and/or retraction ofthe cutting element. The cutting treatment element can furthercomprising a grasper, such as to perform a grasp and cut tissue cuttingprocedure.

The one or more treatment elements used to treat target tissue in STEP43 can be positioned on an elongate shaft, such as an elongate shaftthat passes within a working channel of an endoscope or passes alongsidean endoscope. The elongate shaft can be advanced over a guidewire.

The method of FIG. 1 can include locating or otherwise identifying oneor more anatomical locations such as an anatomical location where energyfrom the tissue treatment element can be reduced or avoided. In someembodiments, one or more anatomical locations identified include theampulla of Vater or the pylorus. In some embodiments, a system fortreating the target tissue includes a visualization element, such isdescribed in reference to system 10 of FIG. 3 herebelow. Tissue can betreated based on an image produced by the visualization element, such asa visible light or other camera. The system can further include a tissueprotection element, also as described in reference to FIG. 3. In someembodiments, tissue is protected with a tissue protection elementcomprising at least one of a thermal barrier and/or a spacer. The tissueprotection element can protect tissue such as the ampulla of Vater. Thetissue protection element can be deployed before one or more segmentsare target tissue as treated, such as one or more tissue segmentsproximate the ampulla of Vater. The tissue protection element can bedeployed prior to the treatment of any target tissue. In someembodiments, a tissue protection element is removed from the patient,such as during or after the treatment of one or more segments of targettissue. Alternatively or additionally, a tissue protection element canbe constructed and arranged to be evacuated by the patient's GI system.

Referring now to FIG. 1A, a perspective view of a tissue surface and anenergy delivery zone is illustrated, consistent with the presentinventive concepts. Tissue surface S1 is shown as a flat surface forillustrative clarity, however tissue surface S1 can comprise arelatively flat and/or multi-dimensional tissue surface, such as aninner (full or partial) circumferential surface of the esophagus,duodenum, jejunum, ileum and/or colon. Tissue surface S1 can comprisetissue of the mouth or stomach, or any location of the GI tract or otheranatomical location. Positioned on surface S1 is an energy delivery zoneEDZ1. At least a portion of energy delivery zone EDZ1 has been selectedfor receiving energy to treat target tissue, such as is described inSTEP 20 or another step of the method of FIG. 1 described hereabove.Energy delivery zone EDZ1 can receive energy in a single energy deliveryor multiple energy deliveries. Energy delivery zone EDZ1 can be one ofmultiple energy delivery zones treated in one or more clinicalprocedures to treat a patient disease or disorder as described herein.

Energy can be delivered to a continuous surface, or to multiple discretesurfaces, such as surfaces S_(E) as shown. Surfaces S_(E) are shown notto scale (neither size nor relative positioning) for illustrativeclarity. In some embodiments, the majority (e.g. greater than 50% orgreater than 70% or greater than 90%) of energy delivery zone EDZ1receives energy. In other embodiments, a small proportion of energydelivery zone EDZ1 receives energy, such as with a fractional energydelivery provided to less than 50% of the area of energy delivery zoneEDZ1, such as less than 20%, less than 10%, less than 5%, or less than2% of the area of EDZ1. In some embodiments, a fractional energydelivery is provided to less than 1% of the area of EDZ1. In someembodiments, a fractional energy delivery is delivered to one or moreaxial segments of GI tissue in multiple passes (e.g. a first one or moreenergy deliveries to an axial segment of GI tissue followed by a secondone or more energy deliveries to a similar axial segment of GI tissue).Referring additionally to FIG. 1B, a side sectional view of a portion ofthe energy treatment zone EDZ1 of FIG. 1A along line A-A is illustrated.Energy delivered to surfaces S_(E) result in the creation of multipletreated target tissue volumes TT1, which each have a proximal surfaceS_(TT). Each treated target tissue TT1 extends through the mucosal layerof the tubular tissue, and at least partially into the submucosal layerwhile avoiding damage to deeper layers. Due to heat conduction, the areaof each surface S_(TT) is greater than the area of each correspondingsurface S_(E). Surfaces S_(TT) are separated by a distance d_(S) ofnon-treated tissue. In some embodiments, d_(S) is approximately zero,such that surfaces S_(T) share a common boundary. In some embodiments, afractional energy delivery is used such that d_(S) is greater than zero(e.g. d_(S) can be larger than a width of surface S_(TT)) and thecumulative surface areas of S_(TT) within energy delivery zone EDZ1represent less than 50% of the area of energy delivery zone EDZ1, suchas less than 20%, less than 10%, less than 5%, less than 2% or less than1% of the area of EDZ1.

Referring now to FIG. 1C, a perspective view of a tubular segment of GItissue is illustrated, including two energy delivery zones positioned inthe lumen of the tubular segment, consistent with the present inventiveconcepts. A tubular segment of GI tissue, tubular segment GI1 includes alumen with a surface S1. Positioned on surface S1 are two energydelivery zones, EDZ1 and EDZ2 which each comprise a full circumferentialsegment of tissue surface with lengths L1 and L2 respectively. In someembodiments, EDZ1 and/or EDZ2 comprise partial circumferential surfaceportions of tubular segment GI1. In some embodiments, EDZ1 and/or EDZ2comprise a length (L1 and L2 respectively) between 0.5 cm and 3.0 cm. Insome embodiments, EDZ1 and EDZ2 are separated (e.g. axially separated)by a separation distance D_(S), such as a distance less than or equal to1 cm, or less than or equal to 0.5 cm. In some embodiments, separationdistance D_(S) equals approximately zero, such that zones EDZ1 and EDZ2approximately share a common boundary. In other embodiments, energydelivery zones EDZ1 and EDZ2 overlap.

At least a portion of energy delivery zones EDZ1 and EDZ2 have beenselected for receiving energy to treat target tissue, such as isdescribed in STEP 20 or another step of the method of FIG. 1 describedhereabove. Energy delivery zones EDZ1 and/or EDZ2 can receive energy ina single energy delivery or multiple energy deliveries. Energy deliveryzones EDZ1 and EDZ2 can be two of multiple energy delivery zones treatedin one or more clinical procedures to treat a patient disease ordisorder as described herein.

In some embodiments, a high proportion (e.g. greater than 50%) of energydelivery zone EDZ1 and/or EDZ2 receives energy, such as is shown anddescribed in reference to FIG. 1D herebelow. In other embodiments, a lowproportion (e.g. less than 50%) of energy delivery zone EDZ1 and/or EDZ2receives energy, such as is shown and described in reference to FIG. 1Eherebelow.

Referring now to FIG. 1D, a side sectional view of tissue including thetwo energy delivery zones of FIG. 1C is illustrated, after a highsurface area proportion energy delivery has been delivered to targettissue; consistent with the present inventive concepts. FIG. 1D depictsa sectional view of tubular segment GI1 along line B-B of FIG. 1C. Ahigh proportion of energy delivery zones EDZ1 and EDZ2 have receivedenergy, such as approximately 100% of EDZ1 and EDZ2, such as that theentire length L1 and circumference of EDZ1 and EDZ2 has received energy,treating target tissue TT1 and TT2 respectively. In some embodiments,one or more hot fluid filled balloons (as are described herein) isbrought into contact with EDZ1 and EDZ2 (simultaneously orsequentially), such as to transfer heat to the majority of EDZ1 andEDZ2. Target tissue TT1 and TT2 comprise a relatively fullcircumferential (e.g. 360°) volume of target tissue with surface areaS_(TT1) and S_(TT2) as shown. Surface areas S_(TT1) and S_(TT2) can havea length greater than the corresponding energy delivery zones lengths,L1 and L2 respectively, due to the conduction of heat in the tissue. Thetreated target tissue TT1 and TT2 can extend through the mucosal layer,and partially into the submucosal layer as shown, avoiding damage todeeper tissue layers. In some embodiments, surface areas S_(TT1) andS_(TT2) share a common boundary B1 as shown in FIG. 1D (e.g. separationdistance D_(S) of FIG. 1C is equal to zero). In some embodiments, targettissue TT1 and TT2 can have overlapping portions, such as overlappingportion OP1 as shown.

Referring now to FIG. 1E. a side sectional view of tissue including aportion of a first energy delivery zone of FIG. 1C is illustrated, aftera low surface area proportion energy delivery has been delivered totarget tissue; consistent with the present inventive concepts. FIG. 1Edepicts a sectional view of tubular segment GI1 along line B-B of FIG.1C. A low proportion of energy delivery zone EDZ1 has received energy,such as less than 50% of EDZ1, such as less than 20%, less than 10%,less than 5%, less than 2% or less than 1% of EDZ1. In some embodiments,a fractional approach is used to achieve a low surface area proportionenergy delivery. Fractional energy delivery can be performed with laseror other light energy as described in reference to FIG. 5 herebelow, orany other fractional energy delivery approach such as those describedherein. In the fractional energy delivery approach, multiple, relativelysmall volumes of tissue are treated, such as target tissue segments TT1a, TT1 b, TT1 c and TT1 d (collectively TT1) shown in FIG. 1E. Eachtarget tissue segment TT1 includes an inwardly facing surface S_(TT).Each surface S_(TT) includes a sub-portion that received energy (e.g.light energy), surface S_(E).

Each target tissue segment TT1 can be separated from another targettissue segment by non-treated tissue with a length d_(s). In someembodiments, arrays of target tissue segments TT1 are separated bysimilar distances, such as in a symmetrical pattern that covers a fullcircumferential segment of energy delivery zone EDZ1. In otherembodiments, two or more target tissue segments TT1 are separated bydifferent distances (i.e. different lengths d_(s) of non-treatedtissue). In some embodiments, energy delivery zone EDZ1 comprisesbetween 50 and 3000 target tissue segments TT1 per cm², such asapproximately 500 target tissue segments TT1 per cm². In someembodiments, multiple surfaces S_(TT) comprise an equivalent diameterbetween 20 microns and 200 microns. In some embodiments, multiplesurfaces S_(TT) comprise a major axis less than or equal to 100 microns.

The treated target tissue segments TT1 can extend through the mucosallayer, and partially into the submucosal layer as shown, avoiding damageto deeper tissue layers.

Referring now to FIG. 2A, a photograph of a cross section of mammalianduodenal tissue prior to any target tissue treatment is illustrated. Thenative small intestinal mucosal surface has a complex structure that hasevolutionarily adapted to maximize the surface area available forcontact with the nutrient stream and environment of the GI tract. Thiscomplex structure is comprised of plicae circulares (invaginations ofsubmucosa and mucosa that create gross surface irregularity to theintestinal mucosal surface). Microscopically, the mucosal layer alsocontains villi, comprised by the absorptive and secretory cells of themucosa, as well as connective tissue, nerves, vasculature, and lymph.Within each cell of the mucosa, there are additionally microvilli (notvisible), also known as the “brush border,” which further enhances themucosal surface area.

FIGS. 2B and 2C illustrate a cross section of mammalian duodenal tissuesubsequent to a target tissue treatment, consistent with the presentinventive concepts. Images shown refer to histologic specimens ofmammalian tissue after 42 days follow up from the target tissuetreatment of the present inventive concepts. Unlike in FIG. 2A,illustrated are elimination of the submucosa/mucosal invaginations,plicae circulares, as well as blunting of the villi and architecturaldistortion consistent with failure to completely reconstitute the nativevillus structure. These changes are seen even after inflammation hassubsided and the healing process has completed. The consequence of thesechanges is a durable and dramatic reduction in the amount of mucosalsurface available for interaction with the nutrient stream and GI lumenenvironment. The treatment described in the present inventive conceptshas empirically been demonstrated to create a durable alteration to themucosal surface after healing without deleterious damage to underlyingmuscularis propria tissue.

Referring now to FIG. 3, a schematic view of a system for ablating orotherwise treating target tissue is illustrated, consistent with thepresent inventive concepts. System 10 is configured to treat targettissue TT, such as to treat one or more patient diseases or disordersselected from the group consisting of: diabetes; obesity or otherwisebeing overweight; hypercholesterolemia; exercise intolerance; psoriasis;and combinations of these. In the embodiment of FIG. 3, target tissue TTincludes one or more tissue segments within a body lumen of a mammalianpatient as has been described hereabove. In some embodiments, targettissue TT comprises a continuous or discontinuous circumferentialsegment of a duodenum, such as a volume of tissue comprising at least50% of the duodenal mucosa, or at least 67% of the duodenal mucosa. Insome embodiments, target tissue TT comprises a treatment portioncomprising duodenal mucosal tissue and a safety-margin portioncomprising at least an innermost layer of the duodenal submucosa. System10 can be configured to treat the duodenal mucosa while avoiding damageto duodenal adventitial tissue, such as by avoiding damage to tissuebeyond the mucosa, to tissue beyond the superficial submucosa and/or totissue beyond the deep submucosa.

System 10 can include one or more tissue treatment devices, such asfirst treatment device 100 and second treatment device 100′. Firsttreatment device 100 can be used in a first clinical procedure includingtreatment of target tissue, and second treatment device 100′ can be usedin a second clinical procedure including treatment of target tissue, asis described hereabove. In some embodiments, the second clinicalprocedure is performed at least twenty-four hours after the firstclinical procedure. Target tissue treatments performed in the secondclinical procedure can be constructed and arranged based on one or moreoutcomes of the first clinical procedure, also as is describedhereabove. Additional treatment devices can be included, such as toperform a third or other subsequent clinical procedures including targettissue treatments.

First treatment device 100 and second treatment device 100′ can besimilar or dissimilar treatment devices, and can be constructed andarranged to perform similar or dissimilar treatments to similar ordissimilar volumes of tissue. Differences between first treatment device100 and second treatment device 100′ can include but are not limited to:type of ablative treatment provided such as type of energy delivered;type of non-ablative treatment provided; configuration of a treatmentassembly or a treatment element included such as configuration of atreatment assembly or a treatment element included in the treatmentdevice; length of the device; diameter of a portion of the device; andcombinations of these. In some embodiments, first treatment device 100comprises a first treatment element constructed and arranged to delivera different form of energy than a second treatment element of secondtreatment device 100′. Alternatively or additionally, first treatmentdevice 100 can comprise a first treatment element with a differentgeometry (e.g. different diameter, length and/or tissue contact surfacearea or shape), than a second treatment element of second treatmentdevice 100′.

In some embodiments, system 10 can be constructed and arranged as isdescribed in applicant's co-pending U.S. patent application Ser. No.13/945,138, entitled “Devices and Methods for the Treatment of Tissue”,filed Jan. 18, 2013, the contents of which is incorporated by referencein its entirety. In some embodiments, first treatment device 100 and/orsecond treatment device 100′ can be constructed and arranged to ablatetissue, such as with an ablation treatment selected from the groupconsisting of: delivery of thermal energy from a balloon filled withfluid at an ablative temperature; RF energy ablation such as monopolarand/or bipolar RF energy ablation; delivery of an ablative fluiddirectly to tissue; cryoablation; delivery of laser energy; delivery ofsound energy such as subsonic sound energy or ultrasonic sound energy;plasma energy delivery; argon plasma coagulation; microwave energydelivery; delivery of non-laser light energy; and combinations of these.In some embodiments, first treatment device 100 and/or second treatmentdevice 100′ can be constructed and arranged to perform a non-ablativetreatment of target tissue, such as with a non-ablative treatmentselected from the group consisting of: mechanical removal of mucosaltissue; chemical, sclerosant or pharmaceutical injection into thesubmucosa; radioactive seed deposition; chemical spray such as an acidspray; pharmacologic administration such as drug delivery via anagent-eluting balloon; and combinations of these. First treatment device100 and/or second treatment device can be configured to resect tissue,such as to resect tissue selected from the group consisting of: plicaetissue; mucosal tissue; submucosal tissue; and combinations of these.

System 10 can include one or more body introduction devices, such asendoscope 350. Endoscope 350 can comprise a standard GI endoscope suchas an endoscope with one or more working channels configured toslidingly receive first treatment device 100 (as shown) and/or secondtreatment device 100′.

System 10 can include energy delivery unit (EDU) 330, which can beoperably attached to first treatment device 100 (as shown) and/or secondtreatment device 100′. EDU 330 can be configured to provide numerousforms of energy to one or more treatment elements of first treatmentdevice 100 and/or second treatment device 100′, such as an energy formselected from the group consisting of: RF energy; microwave energy;laser energy; sound energy such as subsonic sound energy or ultrasoundenergy; chemical energy; thermal energy such as heat energy or cryogenicenergy; and combinations of these.

System 10 can include pumping assembly 340 which can provide and/orremove one or more fluids from one or more devices of system 10, such asfirst treatment device 100, second treatment device 100′ and/orendoscope 350. Pumping assembly 340 can include one or more fluidreservoirs, such as fluid reservoir 341 shown, and/or it can receive orsupply fluids to EDU 330. In some embodiments, pumping assembly 340and/or EDU 330 recirculate one or more fluids through a device of system10, such as to recirculate fluid through first treatment device 100,second treatment device 100′ and/or endoscope 350.

System 10 can include motion transfer assembly 320, which can beconstructed and arranged to rotate, translate and/or otherwise move oneor more devices, assemblies and/or components of system 10, as isdescribed in detail herebelow.

System 10 can include controller 310, comprising one or more algorithms311, which can be constructed and arranged to automatically and/ormanually control and/or monitor one or more devices, assemblies and/orcomponents of system 10, as is described in detail herebelow.

Ablation device 100 comprises a tissue treatment assembly, treatmentassembly 140. Treatment assembly 140 includes one or more elementsconstructed and arranged to ablate or otherwise treat target tissue,such as treatment element 145 shown. Treatment element 145 can compriseone or more elements selected from the group consisting of: anelectrical energy delivery element such as one or more electrodesconstructed and arranged to deliver RF energy; a fluid delivery elementsuch as a nozzle or permeable surface constructed and arranged todeliver ablative fluid directly to target tissue TT; a balloon such as aballoon constructed and arranged to receive an ablative fluid anddeliver hot or cold thermal energy to ablate target tissue TT; a laserenergy delivery element such as an optical fiber, a focusing lens and/orother optical component; a sound energy delivery element such as apiezo-based element configured to deliver ultrasonic and/or subsonicenergy; a tissue abrading element; and combinations of these. Treatmentelement 145 can be positioned on, in, within and/or passing through oneor more components of treatment assembly 140, such as a balloon, cage,spline or other component as are described in detail herein. In someembodiments, treatment assembly 140 and treatment element 145 are thesame component, such as when treatment assembly 140 comprises a balloonconstructed and arranged to receive hot or cold ablative fluid to treattarget tissue. Treatment assembly 140 can comprise an energydistribution element, such as one or more optical components configuredto rotate, translate and/or otherwise distribute laser or other lightenergy to target tissue. In some embodiments, treatment assembly 140and/or treatment element 145 comprise an energy distribution elementincluding a rotating element such a rotating mirror; a rotating prismand/or a rotating diffractive optic. In some embodiments, ablationdevice 100 comprises one or more fibers that deliver laser or otherlight energy to a treatment element 145 comprising a balloon filled withlight-scattering material, such as is described in reference to FIGS. 5Aand 5B herebelow.

In some embodiments, first treatment device 100 and/or second treatmentdevice 100′ delivers heat or thermal energy to tissue, such as whentreatment assembly 140 and/or treatment element 145 comprises a balloonconstructed and arranged to be filled with an ablative fluid comprisinga hot or cold volume of fluid at a temperature sufficient to ablatetissue when the balloon contacts the tissue. The hot or cold volume offluid can be provided to treatment assembly 140 and/or treatment element145 via EDU 330 and/or pumping assembly 340. System 10 can be configuredto deliver thermal energy to tissue as is described in applicant'sco-pending International Application Serial Number PCT/US2013/28082,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Feb. 27, 2013, the contents of which is incorporatedherein by reference in its entirety.

In some embodiments, first treatment device 100 and/or second treatmentdevice 100′ delivers RF energy to tissue, such as when treatment element145 comprises one or more electrodes constructed and arranged to receiveRF energy provided by EDU 330. In these embodiments, the one or moreelectrodes can comprise one or more conductive dots positioned on anexpandable element such as a balloon. In some embodiments, EDU 330 isconfigured to deliver RF energy to one or more electrodes of firsttreatment device 100 and/or second treatment device 100′, such as in amonopolar mode through a grounding pad such as ground pad 70 and/or in abipolar mode between two or more electrodes of first treatment device100 or second treatment device 100′. System 10 can be configured todeliver RF energy to tissue as is described in applicant's co-pendingInternational PCT Application Serial Number PCT/US2013/052786, entitled“Electrical Energy Ablation Systems, Devices and Methods for theTreatment of Tissue”, filed Jul. 30, 2013, the contents of which isincorporated herein by reference in its entirety.

In some embodiments, first treatment device 100 and/or second treatmentdevice 100′ delivers ablative fluid directly to tissue, such as whentreatment element 145 comprises one or more fluid delivery elements. Inthese embodiments, treatment element 145 can be constructed and arrangedto ablate target tissue TT by delivering ablative fluid provided by EDU330 and/or pumping assembly 340. Treatment element 145 can include oneor more fluid delivery elements selected from the group consisting of:nozzle such as a nozzle configured to deliver a cone or other shapedspray of fluid; opening; hole; slit; permeable membrane; mistingelement; vaporizer; and combinations of these. Ablative fluid cancomprise one or more liquids or gases that are delivered to targettissue TT at a temperature above or below a threshold that would ablatetissue. In some embodiments, the ablative fluid delivered by treatmentelement 145 comprises steam, such as steam at a temperature of 100° C.or above. In some embodiments, the ablative fluid delivered by treatmentelement 145 comprises a vaporized fluid at a temperature below 100° C.,such as a vaporized fluid at a temperature between 70° C. and 90° C. Insome embodiments, the ablative fluid delivered by treatment element 145comprises a gas, such as a gas between 60° C. and 99° C., such as a gasdelivered to tissue at a temperature between 70° C. and 90° C. In someembodiments, the ablative fluid delivered by treatment element 145comprises a vaporized liquid, such as a vaporized liquid delivered totissue at a temperature below 100° C., such as at a temperature between70° C. and 90° C. Alternatively or additionally, an ablative fluiddelivered by treatment element 145 can comprise one or more liquids orgases that cause tissue necrosis or otherwise treat target tissue TT ashas been described hereabove, using one or more chemically active agents(e.g. ablation not primarily caused by delivery or removal of heat fromtissue). In these embodiments, the agent can comprise an agent selectedfrom the group consisting of: sclerotic agent; acid; base; saline;alcohol; carbon dioxide; nitrous oxide; nitrogen; acetic acid; glycerol;and combinations of these. In these embodiments, a counter-acting agentcan be included, such as a counter-acting agent delivered by treatmentdevice 100 or another device or component of system 10 that is used toneutralize, impede, reduce and/or limit tissue ablation caused by thedelivery of a necrotic agent-based ablative fluid. The counter-actingagent can be delivered by treatment element 145 or another component.The counter-acting agent can comprise an agent selected from the groupconsisting of: anti-sclerotic agent; base; acid; buffer solution;saline; water; and combinations of these. System 10 can be configured todeliver ablative fluid directly to tissue as is described in applicant'sco-pending U.S. Provisional Application Ser. No. 61/681,502, entitled“Ablation Systems, Device and Methods for the Treatment of Tissue”,filed Aug. 9, 2012, the contents of which are incorporated herein byreference in their entirety.

As shown in FIG. 3, first treatment device 100 includes coaxial shafts111 a and 111 b. Shaft 111 b has a distal end 112. In some embodiments,distal end 112 includes a bulbous element, ball 113. In theseembodiments, ball 113 can be sized to fit through a working channel ofendoscope 350, such as when ball 113 has a diameter less than 6 mm orless than 4 mm. Alternatively, ball 113 can have a larger diameterconfigured to assist in smoothly traversing plicae, such as a diameterof at least 8 mm. Shafts 111 a and 111 b are sized and configured suchthat shaft 111 a slidingly receives shaft 111 b, such that they can beadvanced and/or retracted in unison or independently. Alternatively,first treatment device 100 can comprise a single shaft. In someembodiments, device 100 comprises a flexible portion (e.g. a portion ofshafts 111 a and 111 b including distal end 112) with a diameter lessthan 6 mm. In some embodiments, the flexible portion is configured topass through a working channel of an endoscope with a diameter of lessthan or equal to 6.0 mm, 4.2 mm, 3.8 mm, 3.2 mm or 2.8 mm. In someembodiments, device 100 comprises a shaft length of 100 cm or longer, orotherwise comprises a length sufficient to be orally and/or nasallyinserted into a patient, and subsequently advanced to reach theesophagus, stomach, duodenum and/or jejunum; and/or rectally insertedinto a patient, and subsequently advanced to reach the terminal ileum ofthat patient. In FIG. 3, shafts 111 a and 111 b have been insertedthrough a working channel (e.g. a 6 mm working channel), lumen 351, ofendoscope 350, typically a GI endoscope. Shafts 111 a and/or 111 b canbe inserted over a standard interventional guidewire, such as guidewire60 shown exiting distal end 112 of shaft 111 b. In an alternativeembodiment, shafts 111 a and 111 b are positioned in a side-by-sideconfiguration, such as to be placed in two separate lumens of endoscope350 or in two other non-coaxial locations. In some embodiments, one orboth of shafts 111 a or 111 b passes through a body lumen or otherinternal body location alongside endoscope 350 (i.e. not through lumen351, traveling relatively parallel with but external to endoscope 350).Shaft 111 a and/or 111 b can include manipulation means configured todeflect and/or steer a distal portion of the shaft, such as via one ormore proximal handle controlled pull wires that extend and are attachedto the distal portion of the shaft (handle and pull wires not shown butwell known to those of skill in the art), such as to deflect and/orsteer treatment assembly 140 and/or expandable assembly 130 towardsand/or away from tissue and/or assist in navigating treatment assembly140 through tortuous anatomy.

Treatment assembly 140 can be positioned on shaft 111 a as shown. Atissue treatment element, treatment element 145 is electrically,fluidly, mechanically and/or otherwise operably connected to conduit141. Conduit 141 comprises one or more elongate filaments selected fromthe group consisting of: a wire such as one or more wires configured todeliver electrical or other power and/or transmit electrical or otherdata signals; an optical fiber such as one or more optical fibersconfigured to deliver power and/or transmit data signals; a tube such asa fluid delivery tube; a control rod such as an advanceable and/orretractable control rod; and combinations of these. Conduit 141 travelsproximally through shaft 111 a and operably attaches to EDU 330, pumpingassembly 340, motion transfer assembly 320 and/or another component,assembly or device of system 10.

In some embodiments, conduit 141 comprises one or more fluid deliverytubes constructed and arranged to deliver and/or recirculate heated orchilled fluid into treatment assembly 140, such as heated or chilledfluid received from EDU 330 and/or pumping assembly 340 and deliveredinto treatment element 145, such as when treatment element 145 comprisesa balloon or other fluid reservoir configured to receive ablative fluidat a temperature sufficient to ablate tissue when treatment element 145contacts the tissue. Alternatively or additionally, conduit 141 cancomprise one or more fluid delivery tubes constructed and arranged todeliver an ablative fluid to treatment assembly 140, such as ablativefluid provided by EDU 330 and/or pumping assembly 340 and delivereddirectly to target tissue TT by one or more treatment elements 145, suchas when treatment element 145 comprises a fluid delivery element such asa nozzle. Conduit 141 can further comprise one or more insulating layersconfigured to prevent transfer of heat into and/or out of conduit 141.Conduit 141 can include a surrounding lumen which receives a circulatingfluid configured to provide an insulating, warming and/or cooling effecton conduit 141 and/or any fluid contained within conduit 141. Conduit141 and/or another fluid delivery tube of system 10 can comprise one ormore elongate hollow tubes, such as a hollow tube positioned withinshaft 111 a. Alternatively, conduit 141 and/or another fluid deliverytube of system 10 can comprise a lumen within a shaft, such as a lumenwithin shaft 111 a. In some embodiments, conduit 141 and/or anotherfluid delivery tube of system 10 comprises both a lumen and a hollowtube, such as when the lumen and hollow tube are fluidly connected in anend-to-end configuration. Conduit 141 typically attaches to EDU 330and/or pumping assembly 340 with one or more operator attachable fluidconnections ports, such as a fluid connection port included in a handlepositioned on the proximal end of shaft 111 a, handle not shown. Conduit141 can comprise one or more fluid delivery tubes including one or morevalves, not shown but such as a duck-bill or other valve used toregulate flow within conduit 141, such as to regulate flow pressureand/or direction.

In some embodiments, conduit 141 comprises one or more elongatefilaments constructed and arranged to transmit energy and/or data.Conduit 141 can comprise one or more wires constructed and arranged todeliver RF energy to one or more electrode-type treatment elements 145,such as when the treatment elements 145 are configured to ablate targettissue TT in monopolar and/or bipolar modes as described herein. Conduit141 can comprise one or more filaments constructed and arranged todeliver laser energy, such as one or more optical fibers constructed andarranged to deliver laser energy to one or more lenses or other opticalcomponent-type treatment elements 145, such as to ablate target tissueTT with laser or other light energy. Conduit 141 can comprise one ormore wires or other energy transfer filaments constructed and arrangedto allow a sound producing-type treatment element to ablate targettissue TT with sound energy such as ultrasonic or subsonic sound energy.Conduit 141 can comprise one or more wires or optical fibers configuredto transmit information, such as information received from a sensor ofsystem 10 as described herebelow.

In some embodiments, conduit 141 comprises one or more control rodsconstructed and arranged to cause one or more treatment elements 145 torotate and/or translate, such as when conduit 141 is operably attachedto motion transfer assembly 320, such as prior to, during and/or afterdelivery of energy to target tissue. In some embodiments, one or moretreatment elements 145 comprise a surface configured to abrade orotherwise disrupt tissue as it is rotated and/or translated by movementof conduit 141. Alternatively or additionally, one or more treatmentelements 145 can deliver energy and/or fluid to tissue, and movement ofone or more control rods of conduit 141 changes the location of thetissue segment receiving the energy and/or fluid. Motion of one or moretreatment elements 145 can be configured to treat a full circumferential(i.e. 360°) segment of tubular tissue, or a partial circumferential(e.g. a 45°-350°) segment of tubular tissue. Motion of one or moretreatment elements 145 can be configured to treat a particular axiallength of tubular tissue, such as a length comprising at least 25% ofthe length of the duodenum, or at least 35% of the length of theduodenum, or at least 50% of the length of the duodenum, or at least 66%of the length of the duodenum; or at least 75% of the length of theduodenum.

Treatment assembly 140 can be radially expandable, similar to expandableassembly 130 described herebelow. System 10 can be configured to allowexpansion of treatment assembly 140 to cause one or more treatmentelements 145 to contact a tissue wall such as a duodenal wall, such aswhen one or more treatment elements 145 comprise a balloon configured toablate tissue with a contained hot or cold fluid, or when one or moretreatment elements 145 comprise an electrode configured to deliver RFenergy to ablate tissue. Treatment assembly 140 can be configured toexpand to a diameter less than the diameter of the target tissue TT,such as when a vacuum is applied to cause the target tissue TT diameterto decrease to make contact with one or more treatment elements 145, ashas been described hereabove. System 10 can be configured to allowexpansion of treatment assembly 140 to cause one or more treatmentelements 145 to be positioned at a fixed distance from the luminal wallof tubular tissue, such as a positioning at a fixed distance of at least250 microns, at least 500 microns, or at least 1 mm from a tissue wall,such as when one or more treatment elements 145 are configured todeliver ablative fluid to the target tissue TT and/or to deliver lightenergy to the target tissue TT. In addition to treating target tissueTT, treatment assembly 140 and/or one or more treatment elements 145 canbe configured in one or more various forms to modify, manipulate,measure and/or diagnose target tissue TT and/or other tubular ornon-tubular tissue.

In some embodiments, treatment element 145 can be further configured toextract fluids, such as to extract previously administered ablativefluids and/or insufflation fluids from a body lumen. Fluid extractioncan be performed prior to, during and/or after treatment of targettissue TT.

EDU 330 and/or pumping assembly 340 can comprise multiple heat or coldsources used to modify the temperature of one or more fluids provided byand/or passing through EDU 330 and/or pumping assembly 340. The heat orcold sources can be at a fixed temperature or they can be variable. Insome embodiments, a first heat or cold source is at a fixed temperatureand a second heat or cold source is at a variable temperature.

In some embodiments, a cooling fluid is delivered, prior to, duringand/or after the treatment of target tissue TT, such as to preciselycontrol target tissue ablation and avoid ablation of non-target tissue.The cooling fluid can be provided by EDU 330 and/or pumping assembly340, and it can be delivered to tissue, such as target or non-targettissue, and/or it can be delivered to a component of system 10 such asto reduce the temperature of a component of treatment assembly 140.Treatment element 145 and/or another component of system 10 can beconstructed and arranged to deliver the cooling fluid to one or moretissue surfaces, such as a cooling fluid delivered to treatment element145 via conduit 141 and configured to reduce the temperature of one ormore volumes of tissue. The ablation provided by system 10 can comprisea non-desiccating or a desiccating ablation. In some embodiments, anon-desiccating ablation is performed for a first portion of targettissue TT such as in a first tissue treatment, and a desiccatingablation is performed for a second portion of target tissue TT such asin a second tissue treatment. Non-desiccating ablations can be performedto treat over-lapping portions of target tissue TT, and/or to avoidcreation of tissue debris if desired. Desiccating ablations can beperformed to achieve a higher thermal gradient, to remove excess tissue,and/or to ablate rapidly if desired.

EDU 330 and/or pumping assembly 340 can be configured to deliver a hotfluid to pre-heat one or more components of system 10. In someembodiments, the one or more components include conduit 141; a fluiddelivery tube such as a tube within shaft 111 a, a fluid delivery lumensuch as a lumen within shaft 111 a; shaft 111 a; treatment element 145;and combinations of these. System 10 can be configured to pre-heat oneor more components by circulating or recirculating hot fluid, such as ahot liquid or gas. In some embodiments, treatment assembly 140 containsand/or treatment element 145 delivers a hot fluid, and one or morecomponents of system 10 are pre-treated with a hot gas. Alternatively oradditionally, system 10 can comprise one or more insulators surroundingone or more conduits, lumens and/or shafts of treatment device 100and/or system 10, such as an insulator surrounding conduit 141 andconfigured to prevent transfer of heat across (e.g. into or out of)conduit 141.

System 10 can be configured to maintain target tissue TT or other tissuebelow a threshold or within a temperature range, such as in aclosed-loop configuration through the use of one or more sensors such assensor 149 of treatment assembly 140 or sensor 139 of expandableassembly 130, each described in detail herebelow. In some embodiments,tissue temperature is maintained below 100° C., such as between 60° C.and 90° C., such as between 65° C. and 85° C. In some embodiments,system 10 is configured to maintain the temperature of target tissue TTat a setpoint temperature. The setpoint temperature can vary over time.System 10 can be configured to deliver energy at a level that increasesand/or decreases over time. In some embodiments, treatment assembly 140is constructed and arranged to cause the temperature of at least aportion of target tissue TT to rapidly rise to a setpoint (e.g. asetpoint between 60° C. and 75° C.). After the target tissue TT reachesthe setpoint temperature, system 10 can deliver energy or otherwisetreat the target tissue TT to maintain the setpoint temperature for anextended time period.

In some embodiments, EDU 330 and/or pumping assembly 340 is configuredto heat or chill one or more fluids, such as one or more ablative fluids331 or other fluids. In some embodiments, treatment assembly 140 isconfigured to heat or chill one or more fluids. Applicable heating andcooling elements include but are not limited to heat exchangers, heatingcoils, peltier components, refrigeration assemblies, gas expansioncoolers, and the like. Heating and cooling can be applied to a source offluid (e.g. fluid reservoir 341), or to fluid that is withdrawn fromdevice 100 (e.g. a recirculating fluid and/or a body extracted fluidsuch as recovered, previously delivered, ablative or insufflatingfluid). EDU 330 and/or pumping assembly 340 can include one or morepumps configured to deliver and/or extract fluid at a particular flowrate, pressure, or other fluid delivery parameter. System 10 can beconfigured to deliver fluid at a sufficiently high temperature to ablatetarget tissue TT, after which a cooling fluid is delivered to removalthermal energy from target tissue TT and/or other tissue, such ascooling fluid delivered for a time period of at least 2 seconds, atleast 5 seconds, at least 10 seconds or at least 20 seconds.

In some embodiments, treatment device 100 further includes a radiallyexpandable assembly, expandable assembly 130, mounted to shaft 111 b. Insome embodiments, treatment device 100 comprises a single shaft, andboth treatment assembly 140 and expandable assembly 130 are mounted tothat single shaft. Expandable assembly 130 can be configured in one ormore various forms to treat, modify, manipulate, measure and/or diagnosetarget tissue TT and/or other tubular tissue. Expandable assembly 130can comprise one or more expandable elements 131, such as one or moreexpandable elements selected from the group consisting of: an inflatableballoon; a radially expandable stent or cage; an array of splines; oneor more radially deployable arms; a spiral or other helical structure; afurlable structure such as a furlable sheet; an unfurlable structuresuch as an unfurlable sheet; a foldable structure such as a foldablesheet; an unfoldable structure such as an unfoldable sheet; andcombinations of these. In some embodiments, expandable assembly 130 isinflatable (e.g. an inflatable balloon), and inflation fluid can bedelivered into expandable assembly 130 via an inflation tube 136.Inflation tube 136 can comprise a lumen of shaft 111 b (or a tube withinshaft 111 b) that travels proximally through shaft 111 b and shaft 111a, such as to receive inflation fluid delivered by pumping assembly 340.Expandable assembly 130 can be positioned distal to treatment assembly140 as shown in FIG. 3, or alternatively, expandable assembly 130 can bepositioned proximal to treatment assembly 140, such as when treatmentassembly 140 is mounted to shaft 111 b and expandable assembly 130 ismounted to shaft 111 a.

Expandable assembly 130 can be configured to seal a body lumen location,such as to create a full or partial occlusive barrier at a locationwithin the duodenum or other location in the GI tract. System 10 can beconfigured to cause a fluid or other seal comprising an occlusivebarrier selected from the group consisting of: a pressure seal; acryogenically applied seal such as an ice ball seal; a vacuum seal; afull circumferential seal; a partial circumferential seal; andcombinations of these. In some embodiments, treatment element 145 treatsa portion of target tissue TT located proximal or distal to theocclusive barrier. System 10 can include multiple expandable assembliesconfigured to seal a body lumen location, such as first expandableassembly which provides a seal at a proximal end of a segment of tubulartissue, and a second expandable assembly which provides a seal at adistal end of the tubular tissue segment. In some embodiments, treatmentelement 145 treats a portion of target tissue TT located between the twosealed locations, such as between two locations of the duodenum, eachduodenal location sealed by an expandable component or assembly ofdevice 100. One or more expandable assemblies can be configured toocclude a first location of a body lumen, followed by subsequentocclusions of one or more different locations within the body lumen.System 10 can be configured to apply a vacuum between two occlusiveelements, such as a vacuum applied by one or more treatment elements145, via one or more functional elements 138 and/or 148 (attached toexpandable assembly 130 and treatment assembly 140, respectively, eachfunctional element described in detail herebelow) and/or by anotherdevice or component of system 10. Applied vacuum can be used to modify(e.g. change the shape of) the tubular tissue between the two occlusiveelements and/or to increase the sealing force and/or thecircumferentiality of the seal. In some embodiments, system 10 isconfigured to deploy a detached-balloon configured to occlude a bodylumen, where the detached-balloon can later be punctured or otherwisedeflated for physiologic removal by the GI tract. Deployed balloons orother occlusive elements of system 10 can be positioned to protecttissue, such as to protect the ampulla of Vater and/or the pylorus fromadverse effects that can be caused by treatment of target tissue TT bytreatment element 145.

In some embodiments, in addition to expandable assembly 130, treatmentassembly 140 can be radially expandable and/or include one or moreradially expandable elements, such as those described hereabove inreference to expandable assembly 130. In some embodiments, treatmentassembly 140 is configured to radially expand and cause treatmentelement 145 to move closer to and/or become in contact with targettissue TT. Expansion of treatment assembly 140 can occur prior to,during and/or after treatment of target tissue TT by treatment element145. Treatment element 145 can be mounted on, within and/or inside of anexpandable assembly, such as on, within and/or inside of an expandableballoon.

In some embodiments, expandable assembly 130 and/or treatment assembly140 comprise a length of at least 10 mm, such as a length between 10 mmand 40 mm, a length between 15 mm and 30 mm, or a length between 20 mmand 25 mm. In some embodiments, expandable assembly 130 and/or treatmentassembly 140 comprise a length less than or equal to 15 mm, such as whenconfigured to treat curvilinear portions of the GI tract. Multipleassemblies positioned on shafts 111 a and/or 111 b (e.g. between two andtwenty treatment and/or expandable assemblies), such as expandableassembly 130 and treatment assembly 140, can be separated along a shaftby a distance less than or equal to 25 mm, such as a distance less thanor equal to 20 mm. This separation distance can comprise the distancebetween a distal end of a tissue contacting portion of a firstexpandable element, and the neighboring proximal end of a tissuecontacting portion of a second expandable element. In some embodiments,expandable assembly 130 comprises a length, and the separation distancebetween expandable assembly 130 and treatment assembly 140 is less thanor equal to the expandable assembly 130 length. In these embodiments,treatment assembly 140 can comprise a similar length to that ofexpandable assembly 130, such as when both expandable assembly 130 andtreatment assembly 140 comprise an ablation element as is describedherebelow.

Expandable assembly 130 can include one or more fluid delivery elements,such as fluid delivery element 132 and/or fluid delivery element 135.Fluid delivery elements 132 and 135 are connected to one or more fluiddelivery tubes (e.g. independent fluid delivery tubes), not shown buttraveling proximally within shafts 111 b and/or 111 a and fluidlyconnected to EDU 330 and/or pumping assembly 340, such as via one ormore ports on a handle of treatment device 100. Fluid delivery elements132 and/or 135 can be rotatable, advanceable and/or retractable, such asvia one or more control shafts, not shown but operably connected tomotion transfer assembly 320. Fluid delivery elements 132 and/or 135 cancomprise a nozzle or other fluid delivery element as described herein.Fluid delivery element 132 can be oriented such that fluid deliveredthrough fluid delivery element 132 is directed toward one or more device100 components or assemblies, such as toward treatment assembly 140 andtreatment element 145 as shown in FIG. 3. Fluid delivery element 132 canbe used to perform various functions such as the washing or removing ofmaterial from a device 100 component, or to cool or warm the temperatureof a device 100 component. Fluid delivery element 135 can be directedtoward or otherwise deliver fluid to tissue proximate device 100. Fluiddelivery element 135 can have its distal end positioned within tissue(e.g. after an advancement), as shown in FIG. 3, such as to deliverfluid to one or more internal tissue layers. Alternatively, fluiddelivery element 135 can have its distal end positioned in a body lumen,such as to deliver fluid to at least initially contact a tissue surfacesuch as the wall of the duodenum. Fluid delivery element 135 can beconfigured to deliver a fluid to expand tissue. Alternatively oradditionally, a separate submucosal or other tissue expansion device canbe included, such as tissue expansion device 200. Fluid delivery element135 and/or tissue expansion device 200 can be constructed and arrangedto expand tissue as is described in applicant's co-pending InternationalPCT Application Serial Number PCT/US2013/37485, entitled “TissueExpansion Devices, Systems and Methods”, filed Apr. 19, 2013, thecontents of which is incorporated herein by reference in its entirety.Fluid delivery element 135 can be configured to deliver a cooling orwarming fluid to tissue, and/or deliver a fluid configured tocounter-act a chemically caused ablation, as has been describedhereabove. System 10 can include one or more fluids or other material toexpand one or more layers of tissue, such as when tissue expansiondevice 200 includes an injectable tissue-expanding material, such as anon-energy absorbing material and/or an energy-absorbing material suchas water or saline.

Expandable assembly 130 and/or treatment assembly 140 can be configuredto expand to a diameter of at least 10 mm, such as a diameter of atleast 15 mm, at least 20 mm, at least 25 mm, at least 30 mm, or at least40 mm. In some embodiments, expandable assembly 130 and/or treatmentassembly 140 can expand to a diameter between 15 mm and 32 mm. In someembodiments, expandable assembly 130 and/or treatment assembly 140 havetheir diameter controlled by a component of system 10 (e.g. controller310, EDU 330 and/or pumping assembly 340), such as to control thediameter to at least 10 mm, at least 15 mm, at least 20 mm, at least 25mm, at least 30 mm, or at least 40 mm, or to control the diameter to adiameter between 15 mm and 32 mm. Expandable assembly 130 and/ortreatment assembly 140 can be resiliently biased, such as in a radiallyexpanded or radially compacted state. Expandable assembly 130 and/ortreatment assembly 140 can be expanded and/or compacted by a controlshaft. Expandable assembly 130 and/or treatment assembly 140 can beconfigured to achieve a round or non-round shape (e.g. a football shape)when expanded. Expandable assembly 130 and/or treatment assembly 140 canapproximate a tubular shape when expanded, such as a relatively constantdiameter or varying diameter tube shape. Expandable assembly 130 and/ortreatment assembly 140 can be configured to un-fold to a radiallyexpanded state, or to fold to a radially compacted state.

Expandable assembly 130 can comprise at least one functional element138, and treatment assembly 140 can comprise at least one functionalelement 148. Functional elements 138 and/or 148 can be elements selectedfrom the group consisting of: an ablation element such as one or moreelectrodes configured to deliver electrical energy such asradiofrequency (RF) energy; a sensor; a transducer; a fluid deliveryelement such as a needle, a fluid jet, a permeable membrane and/or anexit port; a heating element; a cooling element; and combinations ofthese.

In some embodiments, expandable assembly 130 is configured to ablatetissue, such as via functional element 138. Functional element 138 ofexpandable assembly 130 can comprise one or more ablation elements, suchas those described in applicant's co-pending U.S. patent applicationSer. No. 13/945,138, entitled “Devices and Methods for the Treatment ofTissue”, filed Jan. 18, 2013, the contents of which is incorporatedherein by reference in its entirety. In some embodiments, functionalelement 138 comprises an ablation element selected from the groupconsisting of: an RF energy delivery element such as one or moreelectrodes, each comprising one or more elongate conductors; anultrasonic transducer such as one or more piezo crystals configured toablate tissue; a laser energy delivery element such as one or moreoptical fibers and/or laser diodes; a heat delivery element such as ahot fluid filled balloon; a rotating ablation element; a circumferentialarray of ablation elements; and combinations of these. In theseembodiments, either or both expandable assembly 130 or treatmentassembly 140 can be used to ablate target tissue TT. EDU 330 or anothercomponent of system 10 can be configured to deliver RF or other energyto functional element 138. System 10 can include ground pad 70, such asa standard RF energy delivery ground pad typically placed on thepatient's back, such that EDU 330 can supply RF energy to functionalelement 138 and/or any other electrodes of system 10 in monopolar,bipolar and/or combined monopolar-bipolar energy delivery modes.

In some embodiments, expandable assembly 130 is configured to perform atleast one non-ablative function. Expandable assembly 130 can beconfigured to occlude or partially occlude a lumen surrounded by tissue(as described hereabove), such as a lumen of the GI tract to be occludedduring an insufflation procedure. Expandable assembly 130 can beconfigured to manipulate tissue, such as to linearize and/or distend GItissue by frictionally engaging (e.g. when expanded) and applying forcesto the tissue (e.g. by advancing and/or retracting shaft 111 b). In someembodiments, one or more expandable assemblies 130 can perform afunction selected form the group consisting of: linearizing curvilineartissue; distending tissue; expanding tissue; occluding a body lumen; andcombinations of these. Expandable assembly 130 can be configured to testand/or diagnose tissue, such as when expandable assembly 130 is used tomeasure a diameter of tubular tissue into which it has been inserted.Diameter measurements can be performed in various ways, including butnot limited to: injection of a radiopaque fluid into expandable assembly130 and fluoroscopic measurement of the injected fluid; controlledinflation of expandable assembly 130 to a pressure whose levelcorresponds to a luminal diameter; and combinations of these. In someembodiments, device 100 includes an expandable assembly that can beexpanded with one or more control rods (not shown), such as to perform adiametric measurement of tubular tissue by precision measurement ofcontrol rod advancement (e.g. when control rod position correlates toexpandable assembly diameter). Alternatively or additionally, tubulartissue diameter can be determined by measuring the diameter of anexpandable assembly when it initially, circumferentially contacts thewall of tubular tissue (e.g. when a specific radial force is achievedand/or when contact is observed such as using fluoroscopy or ultrasoundvisualization devices). In some embodiments, system 10 includes aseparate device, such as a balloon catheter, used to perform a diametermeasurement. One or more energy delivery or other ablation parameterscan be adjusted based on the measured diameter of target tissue TTand/or a target tissue segment.

In some embodiments, expandable assembly 130 is configured to expand orotherwise modify one or more layers of tissue, such as when fluiddelivery element 135 and/or functional element 138 comprises a needle,water jet and/or iontophoretic fluid delivery element configured toexpand submucosal tissue of the GI tract, as has been describedhereabove. Alternatively or additionally, system 10 can include aseparate tissue expansion device, tissue expansion device 200. Tissueexpansion device 200 can comprise a reservoir or control means fordelivering a pre-determined amount of fluid to tissue, such as a volumeof fluid of at least 1 ml, or a volume of fluid between 2 ml and 5 ml.Tissue expansion device 200 can be configured to inject fluid intomultiple injection sites (e.g. simultaneously or sequentially), such asa set of multiple injection sites selected from the group consisting of:at least 3 injection sites along a circumference of tubular tissue, afirst injection site separated from a second injection site byapproximately 1 cm, or between 0.5 cm to 5 cm, or between 1 cm and 3 cm,or between 1 cm and 2 cm; two or more injection sites that are axiallyand/or radially spaced; two or more injections sites that are separatedbased on the diameter of the tubular tissue into which they areinjected; and combinations of these. Fluid can be injected with theassistance of one or more vacuum applying elements positioned on or nearfluid delivery elements 132 and/or 135. Injected fluid can comprise amaterial selected from the group consisting of: water; saline; gel; andcombinations of these. In some embodiments, injected fluid comprises aprotein hydrogel.

Tissue expansion can greatly alleviate the need for precision oftreatment, such as precision of delivery of energy and/or precision ofdelivery of an ablative fluid, due to the increased size (e.g. increaseddepth) of the target tissue TT including an associated safety-margin oftissue to which treatment causes no significant adverse event (e.g. anexpanded submucosal layer prior to a mucosal layer ablation).

In some embodiments, expandable assembly 130 and/or treatment assembly140 comprise a shape that can be adjusted by an operator, such as via acontrol rod manipulatable at a proximal handle and/or by motion transferassembly 320. In some embodiments, the shape of the arrangement of oneor more treatment elements 145 can be operator modified by adjusting theshape of treatment assembly 140.

Treatment element 145 can be configured to treat various thicknesses ofGI tissue, such as at least the innermost 500 microns of duodenaltissue, or at least the innermost 1 mm of duodenal tissue. In someembodiments, treatment element 145 can be configured to ablate orotherwise treat a thickness of at least 600 microns, at least 1 mm or atleast 1.25 mm, such as when treating the mucosa of the stomach.Treatment element 145 can be configured to treat a volume of tissuecomprising a surface area and a depth, where the ratio of magnitude ofthe depth to the magnitude of the surface area is less than or equal to1 to 100 (e.g. less than 1%), or less than or equal to 1 to 1000 (e.g.less than 0.1%). In some embodiments, expandable assembly 130 and/ortreatment assembly 140 are configured to be in a relatively rigid state,such as during treatment of target tissue TT.

Treatment element 145 and/or other treatment elements of the presentinventive concepts can be arranged in an array of elements, such as acircumferential or linear array of elements. The circumferential arraycan comprise a partial circumferential array of treatment elements 145,such as an array covering approximately 45° to 300° of circumferentialarea. Partial circumferential arrays of treatment elements 145 can treata first target tissue segment and a second target tissue segment in twosequential steps, where the array is rotated between treatments (e.g.energy deliveries). The circumferential array can comprise a full 360°array of treatment elements 145, such that a full circumferential volumeof target tissue TT can be treated in a single or multiple treatments(e.g. energy deliveries) that do not require repositioning of treatmentassembly 140. In some embodiments, less than 360° of tubular tissue istreated, such as by treating a circumferential portion of tissuecomprising less than or equal to a 350°, or between 300° and 350°, suchas to prevent a full circumferential scar from being created.

Two or more treatment elements 145 can be arranged in a helical array.In some embodiments, at least three, four or five treatment elementsindependently treat target tissue, in similar or dissimilar treatments(e.g. similar or dissimilar amounts of energy, provided simultaneouslyand/or sequentially by EDU 330).

In some embodiments, EDU 330 and/or another device or component ofsystem 10 provides electrical or other energy to a component oftreatment device 100, such as electrical energy provided to a heatingcoil in a distal portion of device 100, now shown but typicallyconnected to one or more wires traveling proximally through shaft 111 a.EDU 330 and/or another device or component of system 10 can provideenergy such as electrical energy to one or more of functional element138 and/or functional element 148 such as when either comprises atransducer or other powered component.

Treatment element 145 can comprise one or more treatment elementsconfigured to treat substantially the entire length of the duodenumsimultaneously and/or without having to reposition treatment device 100,such as when treatment element 145 comprises an array of treatmentelements positioned along substantially the entire length of the targettissue, or when treatment element 145 comprises at least one treatmentelement configured to rotate and/or translate along substantially theentire length of target tissue. Treatment element 145 and/or othertissue treatment elements of the present inventive concepts can beconfigured to treat at least 25% of the entire length of the duodenumsimultaneously and/or without having to reposition treatment device 100.Treatment element 145 and/or other ablation elements of the presentinventive concepts can be configured to treat a first portion of targettissue TT followed by a second portion of target issue TT. The first andsecond treated tissue segments can be overlapping and they can havenon-parallel central axes (e.g. tissue segments in a curved portion ofthe duodenum). Three or more target tissue segments can be treated, suchas to cumulatively ablate at least 25% or at least 50% of the duodenalmucosa.

In some embodiments, expandable assembly 130 and/or treatment assembly140 comprise inflatable or otherwise expandable balloons, such as one ormore of: a compliant balloon; a non-compliant balloon; a balloon with apressure threshold; a balloon with compliant and non-compliant portions;a balloon with a fluid entry port; a balloon with a fluid exit port; andcombinations of these. In some embodiments, expandable assembly 130and/or treatment assembly 140 comprise a balloon which is fluidlyattached to an inflation tube, such as inflation tube 136 which travelsproximally through shaft 111 a and/or 111 b and is attached to aninflation port, not shown but typically attached to a handle on theproximal end of treatment device 100.

In some embodiments, functional element 138 of expandable assembly 130comprises an abrasive element configured for abrading target tissue,such as an abrasive element attached to a balloon or expandable cage.

Shafts 111 a and 111 b can include one or more lumens passingtherethrough, and can comprise wires and/or optical fibers for transferof data and/or energy such as RF energy to functional element 138 and/or148. Shafts 111 b and/or 111 a can comprise one or more shafts, such asone or more concentric shafts configured to deliver and/or recirculatehot and/or cold fluid through expandable assembly 130 and/or treatmentassembly 140, respectively. In some embodiments, a heated fluid is usedto pre-heat one or more treatment device 100 components and/or todeliver a bolus of hot fluid energy, each as described in applicant'sco-pending International Application Serial Number PCT/US2013/28082,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Feb. 27, 2013, the contents of which is incorporatedherein by reference in its entirety. Device 100 can comprise multipleexpandable assemblies 130, such as a first expandable assemblypositioned proximal to treatment assembly 140 (not shown) and a secondexpandable assembly positioned distal to treatment assembly 140(expandable assembly 130 as shown in FIG. 3).

Treatment assembly 140 and/or expandable assembly 130 can be configuredto ablate tissue or otherwise perform a function while positioned in acurved segment of the GI tract, such as is described in reference toFIGS. 4 and 6 herebelow.

System 10 can be configured to ablate or otherwise treat target tissueTT, such as duodenal mucosal tissue, while avoiding damaging non-targettissue, such as the GI adventitia. Target tissue TT can include at leasta portion of safety-margin tissue comprising tissue whose ablationcauses minimal or no adverse effect to the patient, such as sub-mucosaltissue of the GI tract. Target tissue TT can comprise one or moreportions of tissue that are treated simultaneously or sequentially. Insome embodiments, the target tissue TT comprises the majority of thelength of the duodenal mucosa, such as at least 25% or at least 50% ofthe duodenal mucosa. In some embodiments, the target tissue TT comprisesat least 90% of the duodenal mucosa, or at least 95% of the duodenalmucosa. In some embodiments, the target tissue TT includes the fullmucosal thickness of at least a portion of duodenal tissue, as well asat least the innermost 100 microns of submucosal duodenal tissue, or atleast the innermost 200 microns of submucosal duodenal tissue. Thetarget tissue TT can include at least one of ileal mucosal tissue orgastric mucosal tissue.

Endoscope 350 can be a standard endoscope, such as a standard GIendoscope, or a customized endoscope, such as an endoscope includingsensor 353 configured to provide information related to the tissuetreatment of the present inventive concepts. Endoscope 350 can includecamera 352, such as a visible light, ultrasound and/or othervisualization device used by the operator of system 10 prior to, duringand/or after the treatment of target tissue TT, such as during insertionand/or removal of endoscope 350 and/or shafts 111 a and 111 b oftreatment device 100. Camera 352 can provide direct visualization ofinternal body spaces and tissue, such as the internal organs of the GItract. Endoscope 350 can be coupled with or otherwise include aguidewire, e.g. guidewire 60, such as to allow insertion of endoscope350 into the jejunum and/or advancement of treatment device 100.

System 10 can be constructed and arranged to perform insufflation of abody lumen, such as insufflation of a segment of the GI tract. The bodylumen can be pressurized, such as by using one or more standardinsufflation techniques. Insufflation fluid can be introduced throughsecond lumen 354 of endoscope 350. Second lumen 354 travels proximallyand connects to a source of insufflation liquid and/or gas, such aspumping assembly 340, and typically a source of air, carbon dioxide,water and/or saline. Alternatively or additionally, insufflation fluidcan be delivered by treatment device 100, such as through shaft 111 aand/or 111 b, and/or through a port in expandable assembly 130 and/ortreatment assembly 140, such as when functional elements 138 and/or 148,respectively, comprise a fluid delivery port attached to a source ofinsufflation liquid and/or gas (e.g. provided by pumping assembly 340).Alternatively or additionally, a separate device configured to beinserted through endoscope 350 and/or to be positioned alongsideendoscope 350, can have one or more lumens configured to deliver theinsufflation fluid. System 10 can include one or more occlusive elementsand/or devices, such as expandable assembly 130, treatment assembly 140and/or another expandable device configured to radially expand such asto fully or partially occlude a body lumen, such that insufflationpressure can be achieved and/or maintained over time (e.g. reduce orprevent undesired migration of insufflation fluid). The one or moreocclusive elements and/or devices can be positioned proximal to and/ordistal to the luminal segment to be insufflated.

Pumping assembly 340 can be configured to remove fluid from a body lumensuch as a segment of the GI tract. Removed fluids include but are notlimited to: delivered ablative fluid; condensate of delivered ablativefluid; insufflation fluids; excess bodily fluids; chyme; digestivefluids; gas; and combinations of these. Fluids can be removed prior to,during and/or after treatment of target tissue TT by treatment element145. Pumping assembly 340 can be configured to apply a vacuum, such asto remove fluid via at least one treatment element 145, an outflowdrain, or other fluid extraction port of system 10. In some embodiments,extracted fluids are recycled, such as for subsequent delivery by atleast one treatment element 145 to target tissue TT.

Pumping assembly 340 and/or EDU 330 can be configured to deliver one ormore gases (e.g. carbon dioxide, nitrogen, nitrous oxide and/or air) toat least one treatment element 145 or another gas delivering componentof system 10. In some embodiments, at least one treatment element 145comprises a gas jet nozzle configured to deliver gas to target tissue,such as a gas that has been processed to remove moisture or otherwise bedry (e.g. less than the dew point of air, or at a relative humidity lessthan 20% or less than 10%). In some embodiments, system 10 is configuredto deliver gas to cause agitation of an ablative fluid previouslydelivered within a body lumen. System 10 can be configured to deliverdry or other gas to move ablative fluid in a body lumen. The deliveredgas can comprise a cooling gas, such as a gas below 37° C., a gasbetween 0° C. and 7° C. such as a gas between 2° C. and 7° C., and/or agas at approximately 4° C. System 10 can deliver cooling gas for a timeperiod of at least 10 seconds, at least 20 seconds or at least 30seconds. In some embodiments, system 10 delivers cooling gas at atemperature less than 0° C. for a time period less than or equal to 20seconds, less than or 10 seconds, or less than or equal to 5 seconds. Insome embodiments, system 10 is configured to deliver gas at atemperature at or above 42° C., such as to remove moisture or otherwisedry a tissue wall of the GI tract. System 10 can be configured todeliver carbon dioxide gas.

Functional element 138 and/or functional element 148 can comprise asensor. In some embodiments, functional element 138, functional element148, sensor 353 and/or another sensor of system 10, such as sensor 139positioned on expandable assembly 130 and/or sensor 149 positioned ontreatment assembly 140, can comprise a sensor selected from the groupconsisting of: temperature sensors such as thermocouples, thermistors,resistance temperature detectors and optical temperature sensors; straingauges; impedance sensors such as tissue impedance sensors; pressuresensors; blood sensors; optical sensors such as light sensors; soundsensors such as ultrasound sensors; electromagnetic sensors such aselectromagnetic field sensors; visual sensors; and combinations ofthese. The sensors can be configured to provide information to one ormore components of system 10, such as to controller 310 and/or EDU 330,such as to monitor the treatment of target tissue TT and/or to treattarget tissue TT in a closed loop configuration. Energy delivery fromEDU 330 can be initiated, stopped and/or modified based on one or moresensor readings. Algorithm 311 of controller 310 and/or EDU 330 can beconfigured to determine one or more treatment parameters. In someembodiments, algorithm 311 processes one or more sensor signals tomodify an amount of ablative fluid delivered, rate of ablative fluiddelivery, energy delivered, power of energy delivered, voltage of energydelivered, current of energy delivered and/or temperature of ablativefluid or energy delivery. Alternatively or additionally, algorithm 311can comprise an algorithm configured to determine an energy deliveryzone parameter such as an energy delivery zone parameter selected fromthe group consisting of: anatomical location of an energy delivery zone;size of energy delivery zone; percentage of energy delivery zone toreceive energy; type of energy to be delivered to an energy deliveryzone; amount of energy to be delivered to an energy delivery zone; andcombinations of these. Information regarding the energy delivery zoneparameter can be provided to an operator of system 10. This informationcan be employed to set an energy delivery zone parameter, assist theoperator in determining the completion status of the procedure (e.g.determining when the procedure is sufficiently complete) and/or toadvise the operator to continue to complete a pre-specified area orvolume of target tissue. The total area of treatment or number of energydelivery zones or number of treatments during a particular procedure(any of which can be employed in algorithm 311) can be defined bypatient clinical or demographic data, as described herein.

Sensor 149 of treatment assembly 140 can comprise a gravimetric sensor.In these embodiments, sensor 149 can comprise an accelerometer or othersensor configured to provide a signal representing the orientation oftreatment assembly 140 and/or treatment element 145 as it relates to theforce of earth's gravity. In embodiments in which treatment element 145delivers ablative fluid to target tissue TT, the signal provided bysensor 149 can provide information for manual and/or automated controlof ablative fluid delivery direction. In some embodiments, gravimetricorientation of device 100 is provided to an operator, such as via ascreen on controller 310. In some embodiments, the signal from sensor149 is recorded by controller 310, such as to adjust a spray patterndelivered by treatment assembly 140 and/or treatment element 145. Basedon a signal from sensor 149, treatment element 145 and/or shaft 111 acan be positioned to deliver ablative fluid in upward and/or side-ways(i.e. horizontal) directions, such as to allow delivered fluid to flowacross the walls of a lumen in a downward direction. Controller 310 canbe configured to adjust the flow pattern of ablative fluid delivery byadjusting the rotation and/or translation of treatment assembly 140(e.g. by creating an asymmetric movement). Controller 310 can beconfigured to adjust the flow pattern of ablative fluid delivery byadjusting which of multiple treatment elements 145 deliver ablativefluid (e.g. by turning on or more one or more electronic fluid valves)or by adjusting a nozzle direction or nozzle flow path geometry oftreatment element 145 (e.g. when treatment element 145 comprises arotatable nozzle and/or a nozzle with an adjustable orifice). In someembodiments, controller 310 utilizes a signal from sensor 149 tomanipulate one or more treatment elements 145 to deliver fluid in arelatively upward direction. In some embodiments, system 10 includes afluid removal element, such as a treatment element 145 configured toremove fluid or an outflow drain, and the fluid removal element isgravimetrically oriented by a signal provided by sensor 149.

Sensors 139 and/or 149 can comprise a chemical detection sensor, such asa chemical detection sensor to confirm proper apposition of expandableassembly 130 and/or treatment assembly 140. In this configuration, achemical sensor such as a carbon dioxide sensor can be placed distal toexpandable assembly 130 and/or treatment assembly 140, and a fluid suchas carbon dioxide gas can be introduced proximal to the expandableassembly 130 and/or treatment assembly 140. Detection of the introducedfluid by sensor 139 and/or 149 can indicate inadequate apposition ofexpandable assembly 130 and/or treatment assembly 140, respectively.Readjustment to achieve sufficient apposition can prevent inadequatetreatment of target tissue TT (e.g. inadequate transfer of energy)and/or prevent inadequate measurement, modification, manipulation and/ordiagnosis of target tissue TT.

Functional element 138, functional element 148, sensor 139, sensor 149,sensor 353 and/or another sensor of system 10 can be a sensor configuredto provide information related to the tissue treatment performed bytreatment assembly 140 and/or expandable assembly 130, such as a visualsensor mounted to treatment assembly 140 and/or expandable assembly 130that is configured to differentiate tissue types that are proximatetreatment assembly 140 and/or expandable assembly 130. In someembodiments, system 10 is constructed and arranged to differentiatemucosal and submucosal tissue, such as to adjust one or more treatmentparameters (e.g. to stop treatment and/or modify the temperature oftreatment) based on the differentiation. Applicable visible sensorsinclude but are not limited to: visible light camera; infrared camera;CT Scanner; MRI; and combinations of these. In some embodiments, energyprovided by EDU 330 is based on one or more signals from the visiblesensor, such as a sensor providing a signal correlating to tissue colorwherein the energy delivered is modified based on a tissue color change.Sensors 149 and 139 can comprise a sensor configured to provideinformation related to the tissue treatment performed by treatmentassembly 140 and/or expandable assembly 130, respectively, such as atemperature sensor configured to monitor the temperature of treatmentprovided by treatment assembly 140 and/or expandable assembly 130 and/ortissue proximate treatment assembly 140 and/or expandable assembly 130.Sensors 149 and/or 139 can comprise multiple temperature sensors, suchas multiple temperature sensors positioned on treatment assembly 140and/or expandable assembly 130, respectively, with a spacing of at leastone sensor per square centimeter. Energy delivered by EDU 330 can bebased on signals recorded by the multiple temperature sensors.

Functional element 138 and/or functional element 148 can comprise atransducer. In these and other embodiments, functional element 138,functional element 148, and/or another transducer of system 10 can be atransducer selected from the group consisting of: a heat generatingelement; a drug delivery element such as an iontophoretic drug deliveryelement; a magnetic field generator; an ultrasound wave generator suchas a piezo crystal; a light producing element such as a visible and/orinfrared light emitting diode; and combinations of these.

In some embodiments, EDU 330 and/or another device of component ofsystem 10 is configured to deliver a visualizable material, such as avisualizable material delivered to one or more treatment elements 145.In some embodiments, visualizable material is delivered by treatmentelement 145 onto and/or beneath the surface of tissue, to assist in thetreatment of target tissue TT, such as to assess the status of tissueablation. In some embodiments, the visualizable material is selectedfrom the group consisting of; radiopaque agent; ultrasonically visiblematerial; magnetically visible material; and combinations of these. Animaging device of system 10, such as imaging device 410 describedherebelow, can be used to create an image of the visualizable materialduring and/or after delivery of the visualizable material.

In some embodiments, EDU 330 or another device of component of system 10is configured to deliver abrasive particles, such as abrasive particlesdelivered to one or more treatment elements 145. In some embodiments,visualizable material is also delivered by EDU 330 to assist in thetreatment of tissue, such as to improve ablation caused by a mechanicalabrasion treatment.

In some embodiments, EDU 330 is configured to deliver at least RFenergy, and system 10 includes ground pad 70 configured to be attachedto the patient (e.g. on the back of the patient), such that RF energycan be delivered in monopolar delivery mode to one or moreelectrode-based treatment elements 145 of treatment device 100 or to oneor more electrodes of another treatment device of system 10 (e.g. secondtreatment device 100′). Alternatively or additionally, EDU 330 can beconfigured to deliver energy in a bipolar RF mode, such as bipolarenergy delivered between any two electrode-based treatment elements 145of treatment device 100 or between any other two electrodes of anothertreatment device of system 10. Alternatively or additionally, EDU 330can be configured to deliver energy in a combined monopolar-bipolarmode.

EDU 330 can be configured to deliver RF and/or other forms of energy toone or more treatment elements 145 of treatment assembly 140 and/or atreatment element expandable assembly 130. In some embodiments, EDU 330delivers energy selected from the group consisting of: RF energy;microwave energy; plasma energy; ultrasound energy; light energy; andcombinations of these. Energy can be continuous and/or pulsed, and canbe delivered in a closed-loop fashion as described hereabove. Energydelivery parameters such as power, voltage, current and frequency can beheld relatively constant or they can be varied by EDU 330. Energydelivery can be varied from a first tissue location (e.g. a firstportion of target tissue TT) to a second location (e.g. a second portionof target tissue TT), such as a decrease in energy from a first treatedlocation to a second treated location when the second treated locationis thinner than the first treated location. Alternatively oradditionally, energy delivery can be varied during a single applicationof energy to a single tissue location, such as by adjusting one or moreenergy delivery parameters during a continuous energy delivery.Alternatively or additionally, one or more energy delivery parameterscan be varied between a first treatment of target tissue and a secondtreatment of target tissue, for example a first treatment performedduring a first clinical procedure and a second treatment performedduring a second clinical procedure, such as when the second treatment isperformed at least twenty-four hours after the first treatment.

Pumping assembly 340 and/or EDU 330 typically include one or more fluidpumps, such as one or more peristaltic, displacement and/or other fluidpumps; as well as one or more heat exchangers and/or other fluid heatingelements internal and/or external to device 100. Pumping assembly 340and/or EDU 330 can be configured to rapidly deliver and/or withdrawfluid to and/or from treatment assembly 140 and/or expandable assembly130 via one or more fluid transport means. Fluid transport means caninclude a pump configured to deliver fluid at a flow rate of at least 50ml/min and/or a pump and/or vacuum source configured to remove fluid ata flow rate of at least 50 ml/min. In some embodiments, system 10 isconfigured to deliver fluid, such as a liquid, at a flow rate of atleast 500 ml/min, or at least 750 ml/min. A pump and/or vacuum sourcecan be configured to continuously exchange hot fluid and/or to perform anegative pressure priming event to remove fluid from one or more fluidpathways of device 100. Pumping assembly 340, EDU 330, first treatmentdevice 100 and or second treatment device 100′ can include one or morevalves in the fluid delivery and/or fluid withdrawal pathways or one ormore other valves in the fluid pathway within treatment assembly 140and/or expandable assembly 130. Valves can be configured to controlentry of fluid into an area and/or to maintain pressure of fluid withinan area. Valves can be used to transition from a heating fluid, such asa fluid of 90° C. maintained in a treatment assembly for approximately12 seconds, to a cooling fluid, such as a fluid between 4° C. and 10° C.maintained in the assembly element for approximately 30 to 60 seconds.Typical valves include but are not limited to: duck-bill valves; slitvalves; electronically activated valves; pressure relief valves; andcombinations of these. Pumping assembly 340 and/or EDU 330 can beconfigured to rapidly inflate and/or deflate treatment assembly 140and/or expandable assembly 130. Pumping assembly 340 and/or EDU 330 canbe configured to purge the fluid pathways of first treatment device 100and/or second treatment device 100′ with a gas such as air, such as toremove cold and/or hot fluid from the devices and/or to remove gasbubbles from the devices.

EDU 330, treatment element 145 and/or other components of system 10 canbe configured to treat target tissue TT with a non-desiccating ablation,such as by avoiding tissue temperatures above 100° C., avoiding thecreation of steam, or otherwise avoiding deleterious desiccation oftissue. System 10 can be configured to minimize heat production in theoutermost 50% of a mucosal layer, such as to ablate the outermost 50% ofthe mucosal layer via thermal conduction. System 10 can be configured tominimize heat production in the outermost 80% of a mucosal layer, suchas to ablate the outermost 80% of the mucosal layer via thermalconduction. System 10 can be configured to maximize the flow ofelectrical current, such as through the innermost 50% of a mucosallayer, or through the innermost 20% of a mucosal layer. In someembodiments, system 10 can be configured to avoid detachment of tissueparticles.

EDU 330, treatment element 145 and/or other components of system 10 canbe configured to treat target tissue TT such that the temperature of atleast a portion of the target tissue TT rises rapidly, such as at a rateof greater than or equal to 17.5° C. per second. Treatment can bedelivered to cause the temperature of at least a portion of the targettissue TT to reach a setpoint temperature between 60° C. and 90° C.,such as a setpoint temperature between 65° C. and 85° C. System 10 canbe configured to cause the target tissue TT to elevate to a setpointtemperature and maintain that setpoint temperature, such as bymaintaining the setpoint temperature for a time period between 2 and 40seconds. In these embodiments, the setpoint temperature can be between60° C. and 90° C., such as a setpoint temperature between 65° C. and 85°C. that is maintained for between 5 and 15 seconds. In some embodiments,after a setpoint temperature is achieved and/or maintained, thetreatment can be adjusted (e.g. by adjusting energy delivery from EDU330) such that tissue temperature decreases over time, such as to matcha tissue response of the target tissue TT.

Controller 310 can include a graphical user interface configured toallow one or more operators of system 10 to perform one or morefunctions such as entering of one or more system input parameters andvisualizing and/or recording of one or more system output parameters.Controller 310 can include one or more user input components (e.g. touchscreens, keyboards, joysticks, electronic mice and the like), and one ormore user output components (e.g. video displays; liquid crystaldisplays; alphanumeric displays; audio devices such as speakers; lightssuch as light emitting diodes; tactile alerts such as assembliesincluding a vibrating mechanism; and the like). Examples of system inputparameters include but are not limited to: temperature of ablative fluidto be delivered such as temperature of fluid to be delivered to a nozzleor to an expandable reservoir such as a balloon; type of ablative fluidto be delivered; rate of ablative fluid to be delivered; volume ofablative fluid to be delivered; type of energy to be delivered such asRF energy, thermal energy and/or mechanical energy; quantity of energyto be delivered such as a cumulative number of joules of energy to bedelivered and/or peak amount of energy to be delivered; types and levelsof combinations of energies to be delivered; energy delivery duration;pulse width modulation percentage of energy delivered; temperature of acooling fluid to be delivered; temperature of a priming fluid to bedelivered; flow rate of a fluid to be delivered; volume of a fluid to bedelivered; number of reciprocating motions for an energy deliveryelement to transverse; temperature for a treatment assembly such astarget temperature and/or maximum temperature; insufflation pressure;insufflation duration; and combinations of these. System inputparameters can include information based on patient anatomy and/orconditions such as pre-procedural and/or peri-procedural parametersselected from the group consisting of: mucosal density and/or thickness;mucosal “lift” off of submucosa after a submucosal injection;longitudinal location of target tissue within the GI tract; andcombinations of these. Examples of system output parameters include butare not limited to: temperature information such as tissue and/ortreatment assembly temperature information; pressure information such asballoon pressure information and/or insufflation pressure information;force information such as level of force applied to tissue information;patient information such as patient physiologic information recorded byone or more sensors; and combinations of these.

Controller 310 and/or one or more other components of system 10 caninclude an electronics module, such as an electronics module including aprocessor, memory, software, and the like. Controller 310 is typicallyconfigured to allow an operator to initiate, modify and cease treatmentof target tissue TT by the various components of system 10, such as bycontrolling EDU 330 and/or pumping assembly 340. Controller 310 can beconfigured to modify one or more tissue treatment parameters, such as aparameter selected from the group consisting of: temperature of anablative fluid to be delivered directly to tissue or to an expandablereservoir such as a balloon; type of ablative fluid to be delivered;rate of ablative fluid to be delivered; volume of ablative fluid to bedelivered; pulse width modulation on-time and/or off-time; a timedivision multiplexing parameter; and combinations of these. Controller310 can be configured for manual control, so that the operator firstinitiates the tissue treatment, then allows the treatment element 145and/or another associated treatment element to treat the target tissueTT for some time period, after which the operator terminates thetreatment.

Controller 310 and EDU 330 can be configured to treat target tissue TTin constant, varied, continuous and discontinuous energy delivery orother treatment delivery profiles. Pulse width modulation and/or timedivision multiplexing (TDM) can be incorporated to achieve precision ofan ablative treatment, such as to ensure ablation of target tissue TTwhile leaving non-target tissue intact.

In some embodiments, where system 10 is further configured to performhot fluid ablation, controller 310 can be configured to adjust thetemperature, flow rate and/or pressure of fluid delivered to anexpandable reservoir, such as when treatment element 145 and/orexpandable assembly 130 comprise a balloon. Controller 310 can beconfigured to initiate insufflation and/or to adjust insufflationpressure. Controller 310 can be configured to deliver energy orotherwise treat target tissue in a closed-loop fashion, such as bymodifying one or more tissue treatment parameters based on signals fromone or more sensors of system 10, such as those described hereabove.Controller 310 can be programmable such as to allow an operator to storepredetermined system settings for future use.

Controller 310 can comprise an impedance monitoring assembly, such as animpedance monitoring assembly that receives impedance information fromone or both of sensor 139 of expandable assembly 130 and/or sensor 149of treatment assembly 140. EDU 330 can deliver RF energy to one or moreelectrode-based treatment elements of system 10 based on the impedancedetermined by the impedance monitoring assembly.

Numerous embodiments of the systems, methods and devices for treatingtarget tissue TT described hereabove include controlling and/ormonitoring the change in target tissue temperature to cause itsablation, such as a temperature increase above 43° C., typically above60° C., 70° C. or 80° C., to ablate at least a portion of the targettissue TT. One or more cooling fluids can be delivered to limit orotherwise control ablation, such as to prevent damage to non-targettissue, such as the duodenal adventitia. Pumping assembly 340 can beconfigured to deliver a fluid to tissue and/or a component and/orassembly of system 10, such as to warm and/or cool the tissue, componentand/or assembly. Pumping assembly 340 can be configured to deliver acooling fluid to a luminal wall such as the duodenal wall, such as priorto a delivery of energy, during a delivery of energy and/or after adelivery of energy. In some embodiments, a chilled fluid is used to cooltissue prior to, during and/or after a high temperature ablation oftissue. System 10 can be configured to deliver a fluid at a temperaturebelow 37° C. or below 20° C. The chilled fluid can be delivered at atemperature between 0° C. and 7° C., and in some embodiments, thechilled fluid is delivered at a temperature less than 0° C. System 10 tocan be configured to deliver chilled fluid at multiple temperatures totarget tissue TT and/or other tissue. System 10 can be configured todeliver a first chilled fluid at a first temperature for a first timeperiod, followed by a second chilled fluid delivered at a secondtemperature for a second time period. The first and second chilledfluids can be similar or dissimilar fluids, such as similar ordissimilar liquids and/or gases. In some embodiments, the first chilledfluid is colder than the second chilled fluid, such as a first chilledfluid delivered at approximately 4° C. for a time period ofapproximately 5 seconds, followed by fluid delivered at a highertemperature (e.g. a temperature between 10° C. and 37° C.) for a timeperiod of at least 5 seconds. The chilled fluid can be delivered betweentreatment of a first portion of target tissue and a second portion oftarget tissue (e.g. to the same or different tissue), such as to removeresidual heat remaining after the first treatment. The cooling fluid canbe delivered through functional element 138 of expandable assembly 130and/or functional element 148 of treatment assembly 140, such as whenfunctional elements 138 and/or 148 comprises a fluid delivery elementsuch as a nozzle, an exit hole, a slit, or a permeable membrane. Thecooling fluid can be supplied to a location within expandable assembly130 and/or treatment assembly 140, such as when expandable assembly 130and/or treatment assembly 140 comprises a balloon or other expandablereservoir configured to contact tissue. Alternatively or additionally,pumping assembly 340 can be fluidly attached to another component oftreatment device 100 and/or system 10, the attached component not shownbut configured to deliver fluid to tissue and/or a component of system10 such as to add and/or absorb heat. Pumping assembly 340 can comprisea cryogenic source used to deliver fluids at low temperatures, such astemperatures below 0° C. Typical fluids delivered include but are notlimited to: liquids such as water and/or saline; gases such as carbondioxide, nitrogen, nitrous oxide and/or air; and combinations of these.

Pumping assembly 340 can include a desiccant and/or drying assemblyconfigured to dehydrate or otherwise remove moisture from one or moredelivered gases prior to their delivery. In some embodiments, fluidprovided to one or more treatment elements 145 has its temperaturemodified by a component in a distal portion of device 100, such as aheating or cooling element integral or proximal to treatment element 145(e.g. a peltier cooling element, an expanded gas cooling assembly, or aheating coil integral to treatment element 145). Alternatively oradditionally, system 10 can include a component configured to directlycontact tissue in order to cool or warm tissue. In some embodiments,radially expandable assembly 130, functional element 138 and/orfunctional element 148 can be configured to contact tissue and removeand/or add heat from the contacted tissue.

System 10 can include a motion control mechanism, such as motiontransfer assembly 320. Motion transfer assembly 320 can be configured torotate, translate and/or otherwise move a component of system 10, suchas to move one or more of treatment assembly 140, treatment element 145and/or expandable assembly 130. In some embodiments, motion transferassembly 320 is configured to rotate and/or axially translate shafts 111a and/or 111 b such that treatment assembly 140 and/or expandableassembly 130, respectively, are rotated and/or translated. Motiontransfer assembly 320 can be configured to rotate treatment assembly 140and/or expandable assembly 130 independently or in unison. Motiontransfer assembly 320 can be configured to translate treatment assembly140 as treatment is applied to a portion of target tissue TT. In someembodiments, contiguous tissue segments are treated by device 100continuously as motion transfer assembly 320 causes treatment assembly140 to translate at a rate of at least 10 cm per minute, or at a rate ofleast 20 cm per minute. In some embodiments, treatment assembly 140 ismanually translated, such as at a rate of at least 10 cm per minute, orat least 20 cm per minute. Motion transfer assembly 320 can beconfigured to translate treatment assembly 140 between a first tissuetreatment and a second tissue treatment. Motion transfer assembly 320can include one or more rotational and/or linear drive assemblies, suchas those including rotational motors, magnetic drives, lead screw and/orother linear actuators, and the like which are operably connected toshaft 111 a and/or 111 b. Shafts 111 a and/or 111 b are constructed withsufficient column strength and/or torque transfer properties tosufficiently rotate and/or translate treatment assembly 140 and/orexpandable assembly 130, respectively. Motion transfer assembly 320 canbe in communication with controller 310, such as to activate, adjustand/or otherwise control motion transfer assembly 320 and thus themotion of treatment assembly 140 and/or expandable assembly 130. Motiontransfer assembly 320 can be manually driven and/or automatically (e.g.motor) driven. Alternatively or additionally, motion transfer assembly320 can be used to advance and/or retract treatment assembly 140 and/orexpandable assembly 130 from a first position to treat a first portionof target tissue, to a second position to treat a second portion oftarget tissue. In this embodiment, repositioning of treatment assembly140 and/or expandable assembly 130 can be configured to provideoverlapping treatment, such as the overlapping treatment described inreference to FIG. 4 herebelow.

In some embodiments, system 10, first treatment device 100 and/or secondtreatment device 100′ are constructed and arranged to perform afractional treatment of tissue, such as is described hereabove inreference to FIG. 1. First treatment device 100 and/or second treatmentdevice 100′ can be constructed and arranged to treat target tissue witha fractional delivery of RF energy, such as monopolar and/or bipolar RFenergy delivered from an array of electrodes positioned on an expandableelement. In some embodiments, first treatment device 100 and/or secondtreatment device 100′ are configured as a laser or other light energydelivery device constructed and arranged to provide a fractional energydelivery to target tissue, such as device of similar construction todevice 500 of FIGS. 5A and 5B described herebelow. In some embodiments,first treatment device 100 and/or second treatment device 100′ areconfigured to vaporize at least a portion of target tissue.

As described hereabove, system 10 can include one or more additionaltreatment devices, such as second treatment device 100′. Secondtreatment device 100′ and/or other treatment devices of the presentinventive concepts can be configured to treat target tissue TT in thesame clinical procedure, or in a clinical procedure performed at leasttwenty-four hours after the first clinical procedure. Second treatmentdevice 100′ can be of similar or dissimilar construction to firsttreatment device 100. In some embodiments, second treatment device 100′comprises an expandable assembly with a different diameter thanexpandable assembly 130 of device 100. In some embodiments, secondtreatment device 100′ comprises a treatment element with a differentconstruction and arrangement than treatment element 145 of treatmentdevice 100. In some embodiments, second treatment device 100′ comprisesa device selected from the group consisting of: hot fluid filled balloondevice; RF energy delivery device; vapor ablation device; cryoablationdevice; laser ablation device; ultrasound ablation device; mechanicalabrasion device; and combinations of these. Second treatment device 100′can comprise at least one ablation element selected from the groupconsisting of: an RF energy delivery element such as one or moreelectrodes, each comprising one or more elongate conductors; anultrasonic transducer such as one or more piezo crystals configured toablate tissue; a laser energy delivery element such as one or moreoptical fibers and/or laser diodes; a heat delivery element such as ahot fluid filled balloon; a rotating ablation element; a circumferentialarray of ablation elements; and combinations of these.

System 10 can further include one or more imaging devices, such asimaging device 410. Imaging device 410 can be configured to be insertedinto the patient and can comprise a visual light camera; an ultrasoundimager; an optical coherence domain reflectometry (OCDR) imager; and/oran optical coherence tomography (OCT) imager, such as when integral to,attached to, contained within and/or proximate to shaft 111 a and/or 111b. Imaging device 410 can be inserted through a separate working channelof endoscope 350, lumen not shown. In one embodiment, imaging device 410is an ultrasound transducer connected to a shaft, not shown butsurrounded by shaft 111 a and typically rotated and/or translated tocreate a multi-dimensional image of the area surrounding imaging device410. Alternatively or additionally, imaging device 410 can be externalto the patient, such as an imaging device selected from the groupconsisting of: an X-ray; a fluoroscope; an ultrasound image; an MRI; aPET Scanner; a near-infrared imaging camera; a fluorescence imagingcamera; and combinations of these. Image and other information providedby imaging device 410 can be provided to an operator of system 10 and/orused by a component of system 10, such as controller 310, toautomatically or semi-automatically adjust one or more system parameterssuch as one or more energy delivery parameters.

System 10 can further include protective element 191, configured to bepositioned proximate tissue to prevent damage to certain tissue duringtissue ablative fluid delivery, other energy delivery and/or othertissue treatment event. Protective element 191 can comprise an elementselected from the group consisting of: a deployable and/or recoverablecap and/or covering; an advanceable and/or retractable protectivesheath; and combinations of these. Protective element 191 can bedelivered with endoscope 350 and/or another elongate device such thatprotective element 191 can be placed over or otherwise positioned toprotect non-target tissue, such as tissue selected from the groupconsisting of: ampulla of Vater, bile duct, pancreas, pylorus,muscularis externae, serosa; and combinations of these. In someembodiments, protective element 191 is placed prior to treatment of atleast a portion of target tissue TT, and removed in the same clinicalprocedure. In other embodiments, protective element 191 is implanted ina first clinical procedure, and removed in a second clinical procedure,such as a second clinical procedure as described herein. System 10 canbe configured to identify non-target tissue, such as via a camera usedto identify the ampulla of Vater.

System 10 can be configured to prevent excessive distension of theduodenum such as distension that could cause tearing of the serosa. Insome embodiments, system 10 is configured such that all tissuecontacting components and/or fluids delivered by system 10 maintainforces applied on a GI wall below 1.0 psi, such as less than 0.5 psi, orless than 0.3 psi. System 10 can be configured to avoid or otherwiseminimize damage to the muscularis layer of the GI tract, such as bycontrolling pressure of target tissue treatment (e.g. via controllingexpansion force of treatment assembly 140 and or expandable assembly130) and/or by otherwise minimizing trauma imparted on any tissue by oneor more components of system 10.

System 10 can further include one or more pharmaceutical and/or otheragents 420, such as an agent configured for systemic and/or localdelivery to a patient. Agents 420 can be delivered pre-procedurally,peri-procedurally and/or post-procedurally. Agents 420 can comprise oneor more imaging agents, such an imaging agent used with imaging device410. Agents 420 can be one or more pharmaceutical or agents configuredto improve healing, such as agents selected from the group consistingof: antibiotics, steroids, mucosal cytoprotective agents such assucralfate, proton pump inhibitors and/or other acid blocking drugs; andcombinations of these. Alternative or in addition to agents 420,pre-procedural and/or post-procedural diets can be employed, asdescribed herein. For example, pre-procedural diets can include foodintake that is low in carbohydrates and/or low in calories, andpost-procedural diets can include food intake that comprise a totalliquid diet and/or a diet that is low in calories and/or low incarbohydrates.

In some embodiments, system 10 does not include a chronically implantedcomponent and/or device, only body inserted devices that are removed atthe end of the clinical procedure or shortly thereafter, such as devicesremoved within 8 hours of insertion, within 24 hours of insertion and/orwithin one week of insertion. In an alternative embodiment, implant 192can be included. Implant 192 can comprise at least one of: a stent; asleeve; and/or a drug delivery device such as a coated stent, a coatedsleeve and/or an implanted pump. Implant 192 can be inserted into thepatient and remain implanted for a period of at least one month, atleast 6 months or at least 1 year. In some embodiments, a first clinicalprocedure is performed treating target tissue, and a subsequent secondclinical procedure is performed, as is described herein. In these twoclinical procedure embodiments, a device can be implanted in the firstclinical procedure, and removed in the second clinical procedure.

System 10 can include sizing device 430 which is constructed andarranged to be placed into one or more locations of the gastrointestinaltract or other internal location of the patient and measure the size orother geometric parameter of tissue. In some embodiments, sizing device430 comprises a balloon, expandable cage or other sizing elementconstructed and arranged to measure the inner surface diameter of atubular tissue such as duodenal and/or jejunal tissue. A diametermeasurement can be performed by inflating a balloon of sizing device 430to a predetermined pressure and performing a visualization procedure todetermine balloon diameter. Alternatively or additionally, a balloon canbe filled with a fluid and one or more of fluid volume or fluid pressureis measured to determine balloon diameter and subsequently diameter oftubular tissue proximate the balloon. In some embodiments, subsequentapposition of treatment assembly 140 can be determined using thesetissue geometry measurements. Alternatively or additionally, anexpandable element such as a balloon or cage can comprise two or moreelectrodes configured to provide a tissue impedance measurement whosevalue can be correlated to a level of apposition of the expandableelement, and whose expanded diameter (e.g. visually measured)subsequently correlated to a diameter of tubular tissue proximate theexpandable element. In some embodiments, treatment assembly 140 and/orexpandable assembly 130 comprises sizing device 430, such as whentreatment assembly 140 and/or expandable assembly 130 comprise a balloonor other sizing element used to measure a diameter of the inner surfaceof tubular tissue.

Any of the components of system 10 can include a coating, such as alubricious coating. In some embodiments, treatment elements 145 and/orradially expandable elements such as balloons include a lubricious orother material property modifying coating. In some embodiments, aradially expandable treatment assembly 140 and/or expandable assembly130 comprise a hydrophilic coating, for example configured to disperseor otherwise move an ablative fluid.

Each of the components and/or devices of system 10 can be removablyattached to another component, particularly treatment device 100,controller 310, EDU 330, motion transfer assembly 320, pumping assembly340, ground pad 70, endoscope 350 and/or second treatment device 100′.Typical attachment means include but are not limited to mechanical orelectromechanical connectors providing an electrical, optical and/orfluidic connection between the attached components.

Referring now to FIG. 4, a side sectional view of the distal portion ofa treatment device inserted into a curvilinear section of duodenum isillustrated, consistent with the present inventive concepts. Treatmentdevice 100 comprises shaft 110, a relatively flexible, biocompatible,elongate structure configured for insertion into a body lumen such asthe duodenal tissue shown. Shaft 110 is typically connected to a handleon its proximal end, not shown but configured to allow an operator toadvance, retract and otherwise manipulate or control treatment device100. Treatment device 100 can be configured for delivery over aguidewire, via a lumen from a proximal portion to a distal portion, orvia a rapid exchange sidecar in the distal portion of the device(guidewire lumen and sidecar not shown but known to those of skill inthe art). Shaft 110 is shown inserted through introducer 50 which cancomprise an endoscope, sheath, or other body introduction device.

Treatment device 100 further comprises treatment assembly 140, which canbe similar to treatment assembly 140 of FIG. 3. Treatment assembly 140can be expandable and/or it can include one or more expandable elements.Treatment assembly 140 comprises treatment element 145, which isconstructed and arranged to deliver energy to one or more portions of anenergy delivery zone and to treat one or more portions of target tissue.Treatment element 145 can comprise one or more treatment elements suchas a balloon configured to receive sufficiently hot or cold ablativefluid; a fluid delivery element such as a nozzle configured to deliverablative fluid directly onto tissue; one or more electrodes configuredto deliver RF energy to tissue; a light energy delivery element such asa laser light energy delivery element described in reference to FIGS. 5Aand 5B herebelow; and/or other ablation or other tissue treatmentelements such as those described in reference to FIG. 3 hereabove.

Treatment assembly 140 has been positioned in a distal portion ofduodenal tissue, such as a section that includes an expanded segment ofsubmucosal tissue (expansion not shown). Treatment assembly 140 has beenradially expanded such as to contact the mucosal surface of the duodenumat a discrete tissue segment of target tissue, treatment portion 1 asshown. Treatment portion 1 is located distal to a series of sequentialtissue segments of target tissue, treatment portions 2 through 6 asshown. Treatment element 145 is shown in FIG. 4 positioned to ablate orotherwise treat tissue segment 1. Treatment element 145 can be operablyconnected to one or more wires, fluid delivery tubes, or other conduits,not shown but such as conduit 141 of FIG. 3, such that treatment element145 can treat tissue proximate to treatment element 145. As describedabove, each of treatment portions 1 through 6 has a corresponding energydelivery zone (not shown) to which energy is delivered from treatmentelement 145 to cause the appropriate treatment of target tissue.

Treatment assembly 140 can be sized to allow positioning in curvedsegments of the GI tract with a minimum radius of curvature, such as acurved segment of the duodenum and/or jejunum with an average radius ofcurvature less than 5 cm over a 75° arc, or less than 3 cm over a 75°arc, as described herebelow in reference to FIG. 6. In these curvedsegments (and straighter segments as well), treatment assembly 140 canbe expanded without exerting undesired force onto tissue (e.g. expandedto contact the tissue wall and/or to position treatment element 145 afixed distance from the tissue wall). In some embodiments, treatmentassembly 140 is constructed and arranged to treat curved segments of theGI tract and comprises a length less than or equal to 30 mm, such asless than or equal to 25 mm, less than or equal to 20 mm, less than orequal to 15 mm. After treatment of the tissue segment 1, treatmentassembly 140 can be repositioned to tissue segment 2, just proximal tothe tissue segment 1, with or without contracting treatment assembly 140prior to the repositioning. Subsequently, a second tissue treatment(e.g. a second energy delivery) can be performed. The steps ofrepositioning and treating portions of target tissue are repeated untiltissue segments 3, 4, 5, and 6 have been treated. In a single clinicalprocedure, the combined length of target tissue segments 1 through 6 canrepresent between 25% and 100% of the length of the duodenal mucosalength, such as when between 2 and 50 axial segments of tissue receivebetween 2 and 50 energy deliveries from treatment element 145 and/oranother treatment element. In some embodiments, each of tissue segments1 through 6 have a maximum axial length of less than 20 cm, less than 15cm, less than 10 cm, less than 5 cm or less than 3 cm. In someembodiments, the cumulative axial length of tissue segments treated,(e.g. at least segments 1 through 6) is less than 100 cm, or less than50 cm. Alternatively or additionally, other tissue can be treated, suchas has been described hereabove.

Target tissue segments 1 through 6 typically include common oroverlapping tissue segments, such as is shown in FIG. 4. While theembodiment of FIG. 4 shows six target tissue segments being treated,more or fewer segments can be treated. Tissue treatments can beperformed in a contiguous manner (e.g. 1^(st) portion followed by 2^(nd)portion, followed by 3^(rd) portion, etc); however any order can beperformed. In some embodiments, multiple contiguous or discontiguoustissue segments are treated simultaneously. In some embodiments,contiguous tissue segments are treated by device 100 continuously, astreatment assembly 140 is translated proximally and/or distally, such asvia a manual or automated retraction and/or advancement, respectively,as has been described in reference to FIG. 1 hereabove. In someembodiments, treatment of target tissue is performed as treatmentassembly 140 translates at a rate of at least 10 cm per minute. In someembodiments, a segment of non-treated GI tissue is positioned betweentwo segments of treated GI tissue, such as a non-treated segment of GItissue in a sharp bend, such as is described in reference to FIG. 6herebelow.

Referring now to FIGS. 5A and 5B, side and side sectional views of thedistal portion of a light-energy delivering tissue treatment device isillustrated, consistent with the present inventive concepts. Treatmentdevice 500 comprises a shaft 511, typically a flexible shaft includingone or more lumens and configured to be inserted into a patient, such asinto the gastrointestinal tract via the patient's mouth. Shaft 511 canbe advanced through or alongside an endoscope and/or over a guidewire,endoscope and guidewire not shown but such as is described in referenceto FIG. 3 hereabove. Positioned on the distal end of shaft 511 istreatment assembly 540. In some embodiments, shaft 511 passes throughall or a portion of treatment assembly 540, not shown but such as whentreatment assembly 540 is positioned on a distal portion but proximal tothe distal end of shaft 511 (e.g. similar to the positioning oftreatment assembly 140 on shaft 111 b of FIG. 3).

Treatment assembly 540 includes treatment element 545, an energydelivery element constructed and arranged to deliver laser or othertissue treating light configured to treat target tissue. Treatmentelement 545 is operably attached to conduit 541. Conduit 541 can includeone or more filamentous elements selected from the group consisting of:conductive wires; optical fibers; rotatable shafts; fluid deliverylumens; insulating layers; and combinations of these. Treatment assembly540 further includes an inflatable element, balloon 543, which surroundstreatment element 545 and can be radially expanded, such as by thedelivery of one or more fluids to balloon 543 via a fluid delivery tubeof conduit 541. Treatment assembly 540 can be configured to be expanded(e.g. balloon 543 expanded), such as to move closer to and/or contact anenergy delivery zone of the present inventive concepts, such as anexpansion performed prior to a delivery of laser or other light energyto treat target tissue proximate balloon 543.

Treatment assembly 540 and treatment element 545 can be constructed andarranged to fractionally deliver laser or other light energy to tissue,such as is described in reference to the fractional delivery of energydescribed in reference to FIGS. 1 and 3 hereabove. In some embodiments,fractional delivery is achieved by balloon 543 selectively passing lightenergy delivered by treatment element 545. Alternatively oradditionally, fractional delivery can be achieved by treatment element545 delivering one or more rays of light energy that each contact anenergy delivery zone with a limited diameter (e.g. focused light), suchas a single ray of light delivered in a scanning (e.g. rotating and/ortranslating) fashion, or light delivered from an optical element thatproduces multiple rays of light in an appropriate pattern, such as aredescribed herebelow.

In embodiments where balloon 543 selectively passes light energydelivered by treatment element 545, balloon 543 can be configured as apartial shroud that blocks the majority of light emitted by treatmentelement 545 while selectively passing multiple rays of light energy. Inthese embodiments, balloon 543 can be configured to pass light energythrough one or more apertures 542, such as a grid pattern of rows and/orcolumns of material transparent or at least partially transmissive toone or more wavelengths of light configured to treat target tissue,while the remaining portions of balloon 543 block (i.e. preventtransmission of) at least those wavelengths of light.

In embodiments where treatment element 545 is configured to deliver oneor rays of light with limited diameter to tissue, treatment element 545can include one or more optical components configured to focus and/ordistribute the light rays. In these embodiments, all or a majority ofballoon 543 can be transmissive of light emitted from treatment element545.

In the fractional energy delivery approach, a relatively smallproportion of an energy delivery zone receives energy treatment element545. In some embodiments, small portions of the entire surface ofmultiple energy delivery zones receive energy, such as when treatmentassembly 540 is repositioned after each energy delivery zone receives anallotment of light energy. In some embodiments, one or more energydelivery zones have an area between 1 cm² and 5 cm².

The small portions of an energy delivery zone receiving energy result inmultiple treated target tissue segments that each includes an inwardfacing surface relatively positioned on the tissue surface receiving theenergy. In some embodiments, the inward facing surfaces comprise anelliptical geometry, such as a circular geometry. Non-target or othertissue not receiving energy can be positioned between the multipletreated target tissue segments. These treated target tissue segmentsextend into the tissue, such as deeper into the wall of tubular tissuesuch as deeper through a mucosal layer and at least partially into asubmucosal layer. In some embodiments, these treated target tissuesegments including mucosal and submucosal tissue result in reshaping themucosa and/or submucosa. Alternatively or additionally, this fractionaltreatment of the target tissue segments can reduce the submucosalsurface area on which new mucosal tissue subsequently grows. In someembodiments, the target tissue segments inward facing surfacescollectively comprise a quantity of 50 to 3000 per square centimeter oftissue surface receive energy, such as approximately a quantity of 500per square centimeter. The target tissue inward facing surfaces can eachcomprise a surface with an equivalent diameter of between 20 and 200microns (i.e. a surface whose area is equivalent to a circle with adiameter between 20 and 200 microns). The target tissue inward facingportions positioned within an energy delivery zone can be treatedsequentially, such as a sequential energy delivery by treatment element545, when treatment element 545 comprises a scanning light deliveryelement. Alternatively or additionally, multiple target tissue inwardfacing portions positioned within an energy delivery zone can be treatedsimultaneously, such as when light delivered by treatment element 545delivers light to tissue through one or more apertures 542.

A set of energy delivery zones can each comprise an axial length ofbetween 0.5 and 3 cm in length. A treatment assembly 540 can betranslated between energy deliveries, such as a translation ofapproximately between 0.5 cm and 3 cm, such as to allow a slight overlapbetween any two energy delivery zones, such as to cause a mating ofboundaries of any two energy delivery zones and/or such as to provide agap between any two energy delivery zones.

In a fractional approach, the ratio of energy delivery zone tissuereceiving energy to energy delivery zone tissue not receiving energy canbe between 0.1% and 90%, such as less than 50%, less than 20%, less than10%, less than 5%, less than 2% or less than 1%. The target tissuesegment inward facing surfaces can comprise a major axis of less than orequal to 100 microns. The target tissue can be exposed to a temperaturegreater than or equal to 60° C., between 60° C. and 80° C., or atemperature greater than or equal to 100° C. In some embodiments, atleast a portion of the target tissue is vaporized.

In some embodiments, treatment element 545 comprises a laser or otherlight energy source and/or is optically or otherwise coupled to a lightenergy source (e.g. EDU 330 of FIG. 3), such as via conduit 541. In someembodiments, the light source comprises a laser source selected from thegroup consisting of: CO2; Erbium; fiber laser; solid state crystal lasersuch as a Ho:YAG laser; semiconductor laser; and combinations of these.In some embodiments, treatment element 545 delivers light with awavelength selected from the group consisting of: 2.0 to 2.2 micron; 1.8to 2.0 micron; 1.24 to 1.64 micron; and combinations of these. Treatmentelement 545 can be constructed and arranged to deliver light energy inan array of light beams and/or to include an energy distribution elementcomprising a rotating element such as a rotating mirror; prism;diffractive optic; and combinations of these. Treatment element 545 cancomprise one or more optical components, such as an array of lensesconstructed and positioned to distribute multiple rays of light energy.An array of lenses can include two or more lenses selected from thegroup consisting of: holographic lens; fresnel lens; and combinations ofthese.

In some embodiments, treatment element 545 comprises a light-scatteringmaterial 544, such as to scatter light within balloon 543, such as tocause uniform distribution of light through apertures 542. In someembodiments, light-scattering material 544 is positioned outsidetreatment element 545 but within balloon 543, such as when balloon 543is inflated with light-scattering material 544. Light-scatteringmaterial 544 can comprise a fluid or otherwise flowable medium includingone or more of: reflective polystyrene particles; aluminum flakes; andreflective microspheres.

In some embodiments, conduit 541 comprises one or more fibers configuredto deliver laser light with a high-water absorption wavelength (e.g. 1.9or 2.1 microns) delivered to balloon 543 to be scattered vialight-scattering material 544 through apertures 542. Balloon 543 can becoated with opaque paint and apertures created during the manufacturingprocess where salt or other dissolvable material is mixed in with theopaque paint and subsequently dissolved after the paint is dry. The sizeof the salt crystals used can be configured to create correspondinglysized apertures.

Referring now to FIG. 6, a side sectional view of the distal portion ofa treatment device inserted into a curvilinear section of the GI tractis illustrated, consistent with the present inventive concepts. A GItract portion, tubular segment GI1, includes one or more portions to betreated, such as one or more portions selected in the method of FIG. 2described hereabove. One or more curvilinear portions of tubular segmentGI1 (e.g. those comprising a sharp bend) can be selected to not receivetreatment (e.g. segments that do not include an energy delivery zone).As shown, treatment device 100 has been inserted into segment GI1.Treatment device 100 comprises shaft 110, a relatively flexible,biocompatible, elongate structure configured for insertion into a bodylumen such as the duodenal tissue shown. Shaft 110 is typicallyconnected to a handle on its proximal end, not shown but configured toallow an operator to advance, retract and otherwise manipulate orcontrol ablation device 100. Treatment device 100 can be configured fordelivery over a guidewire, via a lumen from a proximal portion to adistal portion, or via a rapid exchange sidecar in the distal portion ofthe device (guidewire lumen and sidecar not shown but known to those ofskill in the art). Shaft 110 can be inserted through an introducercomprising an endoscope, sheath, or other body introduction device, suchas introducer 50 of FIG. 4 described hereabove.

Treatment device 100 further comprises treatment assembly 140, which canbe similar to treatment assembly 140 of FIG. 3. Treatment assembly 140can be expandable and/or it can include one or more expandable elements.Treatment assembly 140 comprises treatment element 145, which isconstructed and arranged to deliver energy to one or more portions of anenergy delivery zone and to treat one or more portions of target tissue.Treatment element 145 can comprise one or more treatment elements suchas a balloon configured to receive sufficiently hot or cold ablativefluid; a fluid delivery element such as a nozzle configured to deliverablative fluid directly onto tissue; one or more electrodes configuredto deliver RF energy to tissue; a light energy delivery element such asa laser light energy delivery element described in reference to FIGS. 5Aand 5B hereabove; and/or other ablation or other tissue treatmentelements such as those described in reference to FIG. 3 hereabove.

Tubular segment GI1 includes at least three energy delivery zones, EDZ1,EDZ2 and EDZ3, which are selected for treatment, such as by receivingenergy from treatment assembly 140 in a series of energy deliveries asdescribed in reference to FIG. 4 hereabove. In some embodiments, one ormore curvilinear portions of tubular segment GI1 are not treated (e.g.those segments do not include an energy delivery zone), such ascurvilinear segment CS1 and/or curvilinear segment CS2 as shown. In someembodiments, one or more axial segments of tissue in a curvilinearportion of duodenal or other gastrointestinal tissue is not treated) ifthe one or more axial segments comprise a curvilinear portion with anapproximate average radius of curvature less than 5 cm over a 75 degreearc. In some embodiments, curvilinear segment 1 comprises an averageradius of curvature less than 5 cm over a 75 degree arc and is nottreated. In some embodiments, curvilinear segment 2 comprises an averageradius of curvature greater than 5 cm over a 75 degree arc and istreated (i.e. includes a fourth energy delivery zone, not shown). Insome embodiments, an axial segment of tissue proximate to the ampulla ofVater can be specifically excluded from an energy delivery zone to avoiddamage to this structure.

As shown in FIG. 6, treatment assembly 140 has been positioned in energydelivery zone EDZ2, such as to deliver energy to an axial segment ofenergy delivery zone EDZ2. Treatment assembly has treated and/or willdeliver energy to all surfaces of energy delivery zones EDZ1, EDZ2 andEDZ3, such as via advancement or retraction between energy deliveries ashas been described herein, such that the selected target tissue ofsegment GI receives proper treatment.

Referring now to FIGS. 7A, 7B and 7C, end sectional views of a tubularsegment of GI tissue are illustrated, prior to tissue expansion, aftertissue expansion and after target tissue treatment, respectively,consistent with the present inventive concepts. In FIG. 7A, tubularsegment GI1 can include a tubular segment of the duodenum and/orjejunum. Tubular segment GI1 can include one or more inner layers L1,and one or more outer layers L2. Layers L1 can include the mucosal layerand one or more inner layers of the submucosa. Layers L2 can include thegastrointestinal adventitia, the tunica serosal, the tunica muscularisand/or the outermost partial layer of the submucosa.

In FIG. 7B, a tissue expansion of one or more layers of layers L1 hasbeen performed, such as a tissue expansion of one or more layers ofsubmucosal tissue performed by a tissue expansion device such astreatment device 100 and/or tissue expansion device 200 of FIG. 3described hereabove. Expansion of layer 1 can create one or more “peaks”and “valleys” on the inner surface of GI1, such as surface peaks L1 _(p)and surface valleys L1 _(v) as shown in FIG. 7B. Also as shown in FIG.7B, a treatment device 100 has been advanced such that treatmentassembly 140 is positioned within tubular segment GI1. Treatment device100 and treatment assembly 140 can be configured as described inreference to treatment device 100 and treatment assembly 140 describedin reference to FIG. 3 hereabove.

In FIG. 7C, treatment assembly 140 has been expanded to contact at leastthe majority of the surface of surface peaks L1 _(p). Energy, such asenergy delivered from a hot fluid balloon or other energy deliveryelement described herein, is delivered from treatment assembly 140 tothe contacted tissue of surface peaks L1 _(p). In some embodiments, atleast a portion of the surface of surface valleys L1 _(v) do not receiveenergy from treatment assembly 140, such that target tissue TT1 includesmultiple partial circumferential tissue segments separated by gaps ofuntreated tissue.

Referring now to FIGS. 8A, 8B and 8C, end sectional views of a tubularsegment of GI tissue are illustrated, prior to tissue expansion, aftertissue expansion and after target tissue treatment, respectively,consistent with the present inventive concepts. In FIG. 8A, tubularsegment GI1 can include a tubular segment of the duodenum and/orjejunum. Tubular segment GI1 can include one or more inner layers L1,and one or more outer layers L2. Layers L1 can include the mucosal layerand one or more inner layers of the submucosa. Layers L2 can include thegastrointestinal adventitia, the tunica serosal, the tunica muscularisand/or the outermost partial layer of the submucosa.

In FIG. 8B, a tissue expansion of one or more layers of layers L1 hasbeen performed, such as a tissue expansion of one or more layers ofsubmucosal tissue performed by a tissue expansion device such astreatment device 100 and/or tissue expansion device 200 of FIG. 3described hereabove. Expansion of layer 1 can create one or more “peaks”and “valleys” on the inner surface of GI1, such as surface peaks L1 _(p)and surface valleys L1 _(v) as shown in FIG. 8B. Also as shown in FIG.8B, a treatment device 100 has been advanced such that treatmentassembly 140 is positioned within tubular segment GI1. Treatment device100 and treatment assembly 140 can be configured as described inreference to treatment device 100 and treatment assembly 140 describedin reference to FIG. 3 hereabove.

In FIG. 8C, treatment assembly 140 has been expanded to contact at leastthe majority of the surface of surface peaks L1 _(p). In someembodiments, treatment assembly 140 makes contact with the majority ofthe surface of surface peaks L1 _(p) and the majority of the surface ofsurface valleys L1 _(v). and/or is configured to deliver energy to themajority of the surface of surface peaks L1 _(p) and the majority of thesurface of surface valleys L1 _(v). Target tissue TT1 comprises a fullcircumferential layer of tissue with non-uniform thickness along itscircumference, such as target tissue whose thickness differs at thelocations of surface peaks L1 _(p) and surface valleys L1 _(v), such asis shown in FIG. 8C.

While the preferred embodiments of the devices and methods have beendescribed in reference to the environment in which they were developed,they are merely illustrative of the principles of the inventions.Modification or combinations of the above-described assemblies, otherembodiments, configurations, and methods for carrying out the invention,and variations of aspects of the invention that are obvious to those ofskill in the art are intended to be within the scope of the claims. Inaddition, where this application has listed the steps of a method orprocedure in a specific order, it may be possible, or even expedient incertain circumstances, to change the order in which some steps areperformed, and it is intended that the particular steps of the method orprocedure claim set forth herebelow not be construed as beingorder-specific unless such order specificity is expressly stated in theclaim.

What is claimed is:
 1. A method for treating a patient comprising:providing a tissue treatment element constructed and arranged to deliverenergy to tissue; and treating target tissue of the patient'sgastrointestinal tract by causing the tissue treatment element todeliver energy to an energy delivery zone; wherein the method causes areduction in the luminal surface area of at least a portion of thegastrointestinal tract.